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THE NATURAL HISTORY OF CANCER 



THE 

NATURAL HISTORY 
OF CANCER 



SPECIAL REFERENCE TO ITS CAUSATION 
AND PREVENTION 



W. ROGER WILLIAMS 

FELLOW OF THE ROYAL COLLEGE OF SURGEONS 



NEW YORK 
WILLIAM WOOD AND COMPANY 

MCMVIII 



PRINTED IN ENGLAND. 



3- lK8- 



All rights reserved 






PREFACE 



THE subject of cancer has hitherto been investigated far too exclusively 
by the pursuit of details in ultimate analysis ; and hardly at all by the 
synthetical and comparative methods, which have been so profitably 
employed in other branches of biological research. 

As that fine pathologist Billroth has remarked : " Everything is too 
hurried nowadays. We suffer from an insatiable craving for new or 
apparently new facts, in the hope of obtaining a possible sensational 
success. No time is allowed to reflect upon, or to reconsider, the onward 
course of scientific inquiry. Where are we ? What have we left behind ? 
What is ahead ? Is it worth while to go farther in this direction or in 
that ? Has detailed work given us a profitable knowledge of, or an 
insight into, the whole subject ? No one finds time to answer such 
questions." 

In order that the immense stores of miscellaneous items of knowledge 
accumulated during the last half-century by dispersive analysis, may be 
profitably utilized for cancer research, concentration is above all things 
necessary ; for only thus can a higher plane of progress be attained. 

Moreover, since the cure of cancer altogether transcends present 
experience, I have in this work specially endeavoured to elucidate the 
causation and prevention of the disease rather than its cure ; for which, 
in my opinion, reliable indications are lacking. 

To this end I have devised and applied a new method of cancer 
research which may be called synthetic whereby I have shown that 
there are modes of life, various habits and so forth, which tend to prevent 
the incidence of cancer almost entirely in healthy stocks, and greatly to 
reduce its ravages, even among those hereditarily predisposed. 

Such are the objects to which the present work is dedicated. 

W. ROGER WILLIAMS. 

CLIFTON, BRISTOL, 

April, 1908. 



ERRATUM 

Page 446, eleventh line from the top : 

" as well as in the veins of the lungs, brain," for " veins ' 
read " bloodvessels." 



CONTENTS 



CHAPTER I 

INTRODUCTION , 

PAGES 

The status of pathology in the scientific hierarchy The meaning of the term 
" natural history," as here employed The term " tumour," and its signifi- 
cance Some generalities de tumoribus " Malignancy," and what is meant 
thereby : a term that covers a multitude of effects Nothing specific about 
malignancy : its physiological prototypes The terms " cancer," " epithelioma " 
(vd carcinoma), and " sarcoma " defined ... . 1-11 



CHAPTER II 
GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 

Preliminary aperqu Some generalities as to the distribution of cancer among 
mankind The influence of race, complexion, and conditions of existence, as 
exemplified by such well-marked racial types as Negroes, North American 
Indians, and Jews General survey of the distribution of cancer in Europe, 
Asia, Australia, Africa, and America - - - 12-49 



CHAPTER III 
THE INCREASE OF CANCER, AND ITS CONCOMITANTS 

The rise of new diseases and the decline of old ones The antiquity of cancer 
Its increase in England and Wales during the nineteenth century, as shown 
by the Registrar-General's data, by life-insurance reports, and by other 
evidence The reality of this increase It has involved all parts of the body, 
without any marked alteration of the old localization ratios The dispropor- 
tionate increase among men The concomitant decline of tubercle JCtio- 
logical considerations : the relation to sudden environmental changes (e.g., to 
urbanization and prosperity in our country, to domestication and alimentation) 
The doctrine of cancer being morbus miseries is refuted The undue preva- 
lence of the disease among the well-to-do and easy-going The increase and 
its concomitants in Scotland, Ireland, Switzerland, Denmark, France, Sweden, 
Holland, Germany, Austria, Italy, United States, Australia, and New 
Zealand --------. 50-78 



CHAPTER IV 
THE TOPOGRAPHICAL DISTRIBUTION OF CANCER 

The researches of Moore and Haviland The persistence of the topographical 
variations in the incidence of cancer in the chief divisions of England and 
Wales during the last half-century These variations are shown to be inde- 
pendent of the diversities in the age and sex distribution of the population 
Reasons for believing that they are mainly the outcome of divergent conditions 
of existence ...-....' 



x CONTENTS 

CHAPTER V 
CANCER AND OTHER TUMOURS IN ANIMALS 

PAGES 

The comparative pathology of tumours still in a backward condition The similarity 
between human and animal tumours : morphological and setiological The 
influence of sex and age The much greater proclivity of domesticated than 
of wild animals to tumours The special frequency of malignant tumours in 
castrated animals of both sexes, and its significance The rarity of malignant 
and other tumours in monkeys : their proclivity to tubercle Malignant and 
other tumours in dogs, cats, horses, mules, asses, oxen, pigs, sheep, goats, 
deer, rabbits, mice, rats, and other mammalian animals ; in birds, reptiles, 
amphibia, and fishes The comparative pathology of the invertebrata is prac- 
tically terra incognita The frequency of quasi -malignant pseudo-plasms in 
animals Tubercle in the animal world ..... 87-114 



CHAPTER VI 
TUMOURS IN VEGETABLE ORGANISMS 

Tumours analogous to those of human and animal pathology, occur also in the 
vegetable world Their relation "to bud formation Adventitious buds and 
bud variation Local hypertrophies Circumscribed non-malignant tumours 
(Knaurs etc.) Woody outgrowths and excrescences " Broussins " constitute 
the nearest approach in vegetable pathology to the malignant tumours of 
human and animal pathology Their special features : illustrative cases The 
great frequency of highly-evolved pseudo-plasms in vegetable organisms : galls 
and other tumour-like new formations : their pathogenesis, development, and 
life-history - - 115-128 



CHAPTER VII 
THE GENESIS OF MALIGNANT TUMOURS 

Historical review. The author's modified cell theory of tumours The present 
controversy Are tumours essentially of intrinsic or extrinsic origin ? The 
general theory of intrinsic pathogenesis Tumour formation as a special form 
of overgrowth of the individual : gemmation Variation, mutation, and tumour 
formation Developmental irregularity, with special reference to the role of 

rests " in the origin of tumours The classification of tumours as (1) teratoid 
(blastogenicj.and (2) histioid (somatogenic) The genesis of teratoid tumours 

-1 he genesis of histioid tumours : congenital defects and tumour formation 
Histioid tumours and pre-natal developmental irregularities, as illustrated by 
the genesis of uterine and mammary tumours - - . 129-168 



CHAPTER VIII 
THE EXPERIMENTAL STUDY OF CANCER GENESIS 

Grafting experiments with normal tissues of pre- and post-natal origin Regenera- 
tive and hyperplastic processes, and their resemblance to cancerous processes- 
Deductions therefrom-Grafting experiments with epidermoidal and connective- 
t ssue structures Grafting entire organs or large parts of the same Implanta 
tion experiments with papillomatous and other non-malignantlumour? with 
special reference to human condylomata and to the contagious venereal tumours 
aoga ine many noxious agents capable of exciting proliferative activitv in 

E m t W ' T irr r ante * eXtm may 6XCite Ce ' tain f^ative reactions 
Experiments with malignant tumours-Jensen's mouse tumour. Grafting 

2H*S'? i J?*5? 1 ani - mas of - the sam ^d different species-Thf 



an 

question as to the transmissibility of cancer between umatem-Auto 
implantation of malignant tumours in man and animals - 169-200 



CONTENTS xi 

CHAPTER IX 

CANCER AND TUMOUR GROWTH IN RELATION TO GROWTH IN 
GENERAL 

PAGES 

The distinction between genesis and growth The growth of ova and tumour germs 
Of growth in unicellular and multicellular organisms The rhythm of growth 
and its relation to the conditions of nutrition in reproduction and tumour forma- 
tion Polarity The essential constituents of a typical cell The integration of 
multicellular organisms The causative factors of growth Parthenogenesis, 
metagenesis, and alternation of generations in relation to nutrition Fertiliza- 
tion and its artificial production : the experiments of Mead, Hertwig, Morgan, 
and Loeb The nucleus : its chromatin and chromosomes Reduction of the 
chromosomes and its significance Tumours as disturbances of the rhythm of 
growth, owing to altered conditions of nutrition Tumour growth, like discon- 
tinuous growth in general, is a disintegrative process The antagonism between 
the forces of growth, development, reproduction, and tumour formation 
Neoplasia as a lapse from predominant gamogenesis in the direction of agamo- 
genesis The reproductive properties of somatic and germ cells are the same 
in kind, and differ only in degree The qualities of malignant and non- 
malignant tumours explained from this standpoint Nutrition and tumour 
growth Cancer in relation to decline of reproductive power ; its special 
frequency after removal of the sexual glands or their destruction by disease 
Metabolism, internal secretions, and cancer The influence of traumata, 
microbes, various chemical, electrical, thermal, mechanical, and other extrinsic 
stimuli The cytological mechanics of tumour growth, with special reference 
to the questions of self-fertilization, reduction of chromosomes, the role of the 
centrosome etc. Chemical researches : the question of specific enzymes etc. 
The failure to demonstrate a specific causative factor for cancer, and its signifi- 
cance Growth, repair, regeneration, and tumour formation - - 201-228 

CHAPTER X 
THE MICROBIC THEORY OF CANCER 

Some general considerations Do all the biological characters of tumours testify 
against their parasitic origin ? The inconclusiveness of the evidence hitherto 
adduced as to the existence of specific cancer microbes The search for a 
definite materies morbi. The " parasitology " of cancer. Bacterial "cancer 
parasites ": the claims of Rappin, Schill, Francke, Schuerlen, Freire, Lampiazi- 
Rubino, Sanarelli, Kiibasoff, Moty, Maragliano, and Doyen General conclu- 
sions as to bacteria. Protozoan " cancer parasites ": the claims of Hake, 
Pfeiffer, Thoma, Darier, Malassez, Albarran, Wickham, Metchnikoff, Soudake- 
wich, Ruffer, Foa, Cattle, Adamkiewicz, Jackson Clarke, D'Arcy Power, Kur- 
loff, Bosc, Plimmer, Leyden, Sjobring, Schiiller, Olt, Bruaudet, Gaylord, 
Feinberg, O. Schmidt, Podvyssotski, Robertson, and Wade General conclu- 
sions as to protozoa. Blastomycetic and mould-like " cancer parasites ": the 
claims of Russell, Sanfelice, Roncali, Maffuci and Sirleo, Corselli and Frisco, 
Busse, Kahane, Curtis, Monsarrat, Leopold, Wlaeff, Skchiwan, Bra, Niessen 
and Braithwaite Blastomycetic dermatitis De Backer's tentatives General 
conclusions as to blastomycetes etc. The question of infection : " cancer 
epidemics," " cancer districts," " cancer houses " etc. - - 229-269 

CHAPTER XI 
INFLAMMATION, TRAUMA, AND OTHER EXTRINSIC FACTORS 

The antithesis of the processes involved in inflammation and tumour growth, with 
demonstration of the fundamental misconception underlying the ancient belief 
as to their identity What is " chronic inflammation " ? The Broussaisian doc- 
trine Is cancer the outcome of inflammation ? Pre-cancerous conditions 
Antecedent inflammatory affections, and cancer of the female breast Child- 
bearing, lacerations, " endometritis " etc., in relation to uterine cancer The 
rarity of cancer of the procident uterus Gastric ulcer and gastric cancer 
Gall-stones and cancer of the gall-bladder Phimosis and cancer of the penis 
" Paget's disease," and cancer of the breast Leucoplasia, syphilis, and 
smoking, in relation to lingual and buccal cancer Traumata and cancer 
" Traumatic malignancy " - - .... 270-288 



xii CONTENTS 



CHAPTER XII 

THE QUESTION OF THE ORIGIN OF MALIGNANT FROM NON-MALIGNANT 
TUMOURS 

PAGES 

The important practical issues involved in this question The ancient belief in the 
liability of non-malignant tumour-like swellings to become malignant, shaken 
by the utilization of the microscope for diagnostic purposes Modern research 
shows that non-malignant tumours have no special proclivity to malignancy 
Discussion of the evidence in detail for some notable examples (e.g., uterine 
myoma, mammary nbro-adenoma, and ovarian cystoma) All kinds of benign 
tumours may exceptionally develop malignancy, but it is shown that none of 
them have any special proclivity that way - - 289-297 



CHAPTER XIII 

MULTIPLE PRIMARY CANCER, AND THE ASSOCIATION OF CANCER WITH 
OTHER TUMOURS 

Although the initial lesion of cancer is generally solitary, yet, of late, many examples 
of primary multiplicity have been reported The like is true of most non- 
malignant tumours, and of the developmental anomalies per excessum 
Bilateral examples of primary multiplicity by no means very exceptional : 
instances in the mamma, ovary, testis, kidney, adrenal, retina etc. Other 
examples of primary multiplicity (e.g., in the skin, uterus, mamma, gastro- 
intestinal tract etc.) General conclusions as to primary multiplicity The 
question of mixed malignant tumours (sarco-epithelioma) The association of 
malignant with non-malignant tumours - - 298-311 



CHAPTER XIV 
THE INFLUENCE OF SEX 

The localization and incidence of tumours (malignant and non-malignant) is much 
influenced by sex Author's analysis of 15,481 consecutive cases Diversities 
in sex incidence are due to biological peculiarities of the affected parts, rather 
than to any general constitutional condition correlated with sex Evidence 
from the national mortality returns as to the sex incidence of cancer Qualifying 
considerations Sex in relation to localization and age incidence - - 312-316 



CHAPTER XV 
THE INFLUENCE OF AGE 

The importance of age incidence in the aetiology of cancer The facts as to the 
age distribution of cancer, as revealed by the national mortality reports, and 
by hospital statistics To appreciate the significance of those facts, some 
knowledge as to the role of age in relation to mortality in general is needed 
Thus regarded, the characteristic feature of the age incidence of cancer is shown 
to be, not its progressive increase with advancing years (for this it shares 
with other lethal maladies), but its disproportionate augmentation in post- 
meridian life Centenarians and other very aged persons are shown to be but 
little prone to malignant tumours Cancer is not a senile disease The special 
feature of the age incidence of cancer is its connexion with the decline in 
reproductive activity Age and sex incidence in respect to localization Early- 
life malignant tumours are sarcomata : pre-natal cases The localization of 
these early-hfe malignant tumours is very different from that of similar tumours 
met with in later life. Malignant epithelial tumours are almost unknown prior 
to puberty and of great rarity under the age of twenty : examples of early- 
life epithehoma in such representative sites as the rectum, stomach, uterus, 
and mamma Resume of the facts and general conclusions - - 317-331 



CONTENTS 



CHAPTER XVI 

/ETIOLOGICAL INDICATIONS DERIVED FROM THE STUDY OF THE LIFE-HISTORY 
OF CANCER PATIENTS 

PAGES 

Nutrition and cancer The cancer type of organization Obesity Blood-pressure 
Diabetes Arthritism and cancer Osteitis deformans Gall-stones The 
inter-relations of tubercle and cancer Pleural adhesions, emphysema, cardiac 
changes etc. Malaria Syphilis and cancer Erysipelas, suppurative affec- 
tions, and infectious diseases Insanity and cancer Grief, anxiety, and 
mental distress The rarity of cancer in prison inmates, paupers, convents etc. 
Dermatoses in the cancerous Paralysed parts and cancer Menstruation 
Alimentation Salt and cancer Alcohol Water Late marriages, decline in 
fertility, celibacy etc. Occupation and social status as influencing the 
proclivity to cancer - 332-355 



CHAPTER XVII 
FAMILY HISTORY 

Physiological heredity, pathological heredity and the vis medicatrix natures 
Darwinism and Weismannism The evidence from the study of disease, 
especially malignant and non-malignant tumours Multiple family cancer : 
remarkable examples in mammary, uterine, gastric, intestinal, ocular, and 
other local forms of cancer Cancer in twins Glioma Instances of the 
inheritance of non-malignant tumours The predominance of homotopic 
transmission Family history analyses Direct, indirect, and atavistic trans- 
mission of cancer Single family prevalence Consanguinity Hereditary pro- 
clivities correlated with cancer, viz., tubercle, insanity, apoplexy, arthritism, 
longevity, and excessive fecundity - - 356-374 



CHAPTER XVIII 

THE INITIAL SEATS OF TUMOURS, AND THEIR RELATIVE FREQUENCY 

Like normal parts of the body, tumours have their own individuality ; hence, in 
studying their life-history, pre-existing structural peculiarities cannot be 
ignored Neoplastic areas are rich in cells still capable of growth and pro- 
liferation Analyses showing the site incidence of tumours, based on 15,481 
hospital cases Tumours seldom originate from obsolete and highly specialized 
structures The initial seats of malignant epithelial tumours, in both sexes, as 
determined by hospital statistics and the national mortality returns The pro- 
clivity of tumours for certain regions of particular organs, as illustrated by the 
uterus, mamma, stomach, intestine, skin etc. The question of trophic nerve 
influence in localization The site incidence of sarcoma and of non-malignant 
tumours and cysts Analytical tables showing the initial seats of malignant 
and non-malignant tumours, and their relative frequency - - 375- 



CHAPTER XIX 
THE MORPHOLOGY OF MALIGNANT TUMOURS 

The primary tumour and its growth The physiological characters of cancer cells : 
their growth and proliferation Nuclear changes : the heterotypical mitosis 
" Ponts intercellulaires " There is nothing specific about cancer cells and 
cancer structures The stroma, lymphatics, bloodvessels, and nerves Chemical 
analysis Enzymes : the question of a special cancer ferment etc. Pre- 
cancerous changes Local dissemination Lymphatic " permeation "- 
Lymph-gland dissemination vi& the thoracic duct The left supra-clavicular 
adenopathy (Troisier's symptom), and its significance General dissemination 
The question of dissemination by non-malignant tumours etc. The similarity 
between the primary tumour and its secondaries The metastases of malignant 
epithelial and connective-tissue tumours contrasted General conclusions as to 
metastasis The theory of metastasis The varieties of malignant tumours 400-453 



xiv CONTENTS 

CHAPTER XX 
RECURRENCE 

PAGES 

Local, lymph-glandular, and raetastatic recurrence Epitheliomatous and sarcoma- 
tous tumours contrasted in respect to their recurrences Some typical examples 
The period at which recurrence supervenes : its variability ; early and late 
recurrences The " recurrence " of ovarian cystoma The frequency of malig- 
nant and non-malignant recurrence after ovariotomy for cystoma The influ- 
ence of diseased, absent, and defective ovaries on recurrence The effect of 
castration The rationale of malignant recurrence - - 454-467 



CHAPTER XXI 

CACHEXIA 

Cachexia may be associated with other morbid conditions besides cancer ; there is, 
therefore, nothing specific about it The cachexia of cancer a consequence of 
the primary tumour It is probably due to toxic albuminoids in the circula- 
tion, derived from the disintegrating cancer cells The blood changes The 
significance of leucocytosis The agglutin reaction No specific opsonin The 
clinical symptoms of cachexia Peripheral neuritis etc. Fatty degeneration 
Osteomalacia The condition of the urine The rarity of amyloid degenera- 
tion and of fever Death by asthenia - - 468-478 



CHAPTER XXII 
QUASI-MALIGNANT PSEUDO-PLASMS 

The difficulties in the diagnosis of cancer, and their causes Chronic inflammatory, 
tuberculous, and syphilitic quasi-malignant lesions Mycotic, microbic, and 
other parasitic pseudo-plasms resembling cancer Examples in mammary and 
cutaneous locations The so-called " withering sarcomata," and the question 
of cancer cures The frequency of similar pseudo-plasms in animals - 479-486 



CHAPTER XXIII 

INFLAMMATION, ULCERATION, RETROGRESSION, AND SPONTANEOUS 
CURE 

The comparative rarity of suppuration of malignant tumours The question of cure 
by ulceiation, sloughing, and gangrene Casoating cancers Retardation, 
arrest, and retrogression Illustrative cases The conditions under which such 
changes occur The starvation treatment of cancer The question of spon- 
taneous cure ........ 487-496 



INDEX OF SUBJECTS ... . 497-507 

INDEX OF NAMES OF AUTHORS CITED - ... . 508-519 



THE NATURAL HISTORY OF CANCER 



CHAPTER I 
INTRODUCTORY 

The Status of Pathology, and the Meaning of the Term " Natural 
History" as here Employed. 

IT may be said of each particular science as of science in general that 
it has been gradually evolved. But this process has affected the various 
sciences very unequally, so that while some have nearly attained the 
highest degree of perfection, others are still in a crude, infantile, or 
undeveloped state. 

In accordance with these ideas, the sciences may be classified in a 
hierarchical manner, according to their state of perfection and degree of 
evolution, with mathematics and astronomy at one end of the series, 
and the biological sciences which include pathology at the other. 

In the intellectual progress of the nineteenth century, the chief event 
has been the translation of these immature biological sciences from the 
domain of empiricism, to their proper place in the scientific hierarchy. 

So far as pathology is concerned, however, this great movement is 
still in its infancy ; for although the medical art has been practised from 
time immemorial, it is only since the beginning of the nineteenth century 
that the crude data thus laboriously acquired, have begun to be treated 
scientifically. There has been no Comte, Spencer, or Darwjn to lighten 
the darkness of modern pathology. \J&*j~ oJn>v$ 1/ti chnJ '. 

It is necessary at the outset to refer thus pointedly to the crudeness 
and immaturity of medical knowledge, because nowhere do these qualities 
find more striking exemplification, than in the terrible welter of disjointed 
facts and contradictory hypotheses, that constitute such a large part of 
modern " tumour science." 

Owing to the progress of knowledge, successive generations view the 
problems presented by the phenomena of disease from different stand- 
points hence every age needs its own interpreters. This is specially 
true of the vast subject of onkology. It will be my endeavour in what 
follows to reduce into some semblance of order these vast masses of 
chaotic materials, and to deduce from them such conclusions as the facts 
seem to warrant. In doing this I shall not scruple to avail myself of 
hypotheses, when these seem likely to aid the investigation ; for, as Comte 

1 



2 THE NATURAL HISTORY OF CANCER 

says : " Si en contemplant les phenomenes, nous ne les rattachions point 
immediatement a quelques principles, non-seulment il nous serait 
impossible de combiner ces observations isolees, et par consequent d'en 
tirer aucun fruit, mais nous serions meme entierement incapables de les 
retenir ; et le plus sou vent les faits resteraient inapergus sous nos yeux." 
The history of every branch of medical knowledge teems with illustrations 
of the truth of this luminous statement. 

By all means let pathologists observe and experiment, but let them 
not neglect to compare, systematize, filiate, and reason on the knowledge 
thus acquired in a disinterested way as if they were dealing with a 
problem of natural history ; and, above all, it must never be forgotten 

V/.that comparison is the great organon of biological, and consequently also 
of pathological, research. 

Hitherto research has been far too exclusively directed to the histo- 
logical, morphological, and experimental conditions of tumours, while 

^the ensemble of their characters and their inter-relations with other 
biological processes have been but little studied. The object of the 
present work is to remedy these defects by giving a right bent to research, 
and a scientific basis to the pathology of cancer and tumour formation. 
To effect this we must work on a broader basis than has hitherto been 

' customary. As Bacon 1 has insisted, in dealing with matters of this 
kind : " The first object must be to prepare a history of the phenomena 
to be explained, in all their modifications and varieties. This history 
should comprehend not only all such facts as spontaneously offer them- 
selves, but all the experiments instituted for the sake of discovery or for 
any other purposes. It ought to be composed with great care ; the facts 
accurately related and distinctly arranged ; their authenticity diligently 
examined ; those that rest on doubtful evidence, though not rejected, yet 
noted as uncertain, with the grounds of the judgment so formed. This 
last is very necessary, for facts often appear incredible only because we 
are ill-informed. This record of facts is Natural History." 

Such is the method I propose to employ in the present undertaking. 

The Term " Tumour." 

It is in consequence of such conditions as those above mentioned, that 
so many of the leading pathological terms are without precise significance. 
Thus the word " tumour," by which we connote the various pathological 
formations with which this work is concerned, has not only been inter- 
preted differently in different ages, but also by authors living in the same 
age, and this diversity is still apparent. A generally acceptable definition 
is, I think, hardly likely to be arrived at, until we have attained more 
uniformity in our conceptions as to the origin and causation of these 
formations. 

By the Latins, who gave us the term, any unusual kind of swelling 

was called " tumor " ; thus Galen and his followers describe : " Tumores 

secundum naturam supra naturam et praeter naturam." In the first 

group they included physiological enlargements, in the second swellings 

1 " Novum Organum," ii. 



INTRODUCTORY 3 

due to displacement of natural parts, while the third embraced all other 
swellings a miscellaneous assemblage, comprising all that has since been 
included under the term " tumour," and many other conditions. 

The tendency of subsequent ages has been to restrict the use of this 
term to a much narrower range. Virchow, however, classed as tumours 
nearly all chronic inflammatory and granulomatous formations, which 
are now generally regarded as being altogether outside this category. 

Recently the term " neoplasm " has obtained currency as a synonym 
for " tumour," for which the old Greek word was 6'y/co<?, whence this 
study has been designated " onkology." 

Many and various are the tentatives that have been made to define 
the term " tumour," but it cannot be said that any of them are really 
satisfactory. No doubt John Hunter realized this when he said : " Of 
all things on the face of the earth definitions are the most cursed " ; and 
Virchow was nearly as emphatic with his famous dictum : " No human 
being can define, even under torture, exactly what a tumour is." Thus 
we reach the conclusion that tumours, like other biological conceptions, 
do not admit of strictly logical definition. 

For practical purposes, however, a tumour may be defined as a 
persistent mass of redundant new formation, not obviously due to any 
extrinsic cause, which grows independently of the body, with which it is 
structurally and functionally uncombined ; so that, although it generally 
assumes a more or less circumscribed form, it is nevertheless distinct 
from any known anomaly. 

From the biological standpoint, tumour formation may be regarded as 
a phenomenon of the same order as reproduction in general that is to 
say, as a special form of overgrowth of the individual. This implies 
^recognition of the affinity between tumour formation and morphological 
variation in general, which has hitherto been generally overlooked, 
much to the detriment of progress in tumour science. It will be main- 
tained in the sequel that, in ultimate analysis, a tumour is the outcome of 
an abortive attempt of certain cells to repeat agamically some portion 
of the normal ontogeny hence individuation is the cardinal feature of 
every tumour. What is variation but a novel kind of cell multiplication ? 
And what is tumour formation but a special variety of this novelty ? 
And is not every variation, as suggested by Virchow, essentially patho- 
logical in origin ? Variation, mutation, and tumour formation what are 
these but different degrees of the same process, w r hich, being maintained 
continuously from the germ to the latest period of life, determines all 
organic formation ? In the sequel it will be shown that the determining 
factor, the true cause of all these variations, is nutrition using the 
term in its widest sense. 

Such is the thesis I now propose to maintain. 

Some Generalities de Tumoribus. 

In investigating the structure and development of tumours, it is 
impossible for the observer to escape the conviction that the phenomena 
met with have their counterparts in the normal evolution. Tumours, 

12 



4 THE NATURAL HISTORY OF CANCER 

like other organic structures, ultimately depend upon the processes of 
growth and reproduction going on in the cells of the part whence they 
originate, whether these are of pre- or post-natal origin. Pathological 
and physiological cells are alike in their morphological and vital properties. 
Cell and nuclear division conform to the physiological type, even as to 
the details of karyokinesis. In both cases the tendency of the newly 
formed cells to revert to the parental type is perfectly obvious, and this 
is specially manifest when the tumour cells become converted into tissues. 
Hence the same tumour can only be found again, in exactly the same 
situation. Thus it happens that throughout the whole range of tumour 
structures no elements of new and specific type can be found, but we 
everywhere meet with structures which resemble the physiological struc- 
tures, both genetically and histologically. In short, tumours are never 
of such a monstrous nature, as not to present some analogy with the corre- 
sponding pre-existing structures of the part whence they originate, either 
in their embryonic or post-embryonic states. Hence no study of the life- 
history of tumours can be complete, which ignores pre-existing structural 
peculiarities. 

But behind these structural changes we must remember there always 
are functional changes, although ordinarily we hear very little of them 
in connexion -with modern studies on tumour genesis. We may, however, 
be certain that tumours, like other morphological variations, are ulti- 
mately the outcome of the interactions of function and structure. 

Tumours grow and are nourished like normal parts of the body, yet, 
in return for the nutriment thus supplied, they contribute to it nothing 
useful ; indeed, their relation to the rest of the organism differs but little 
from that of parasitism. 

Malignancy. 

Even if pathology were as highly perfected as botany and zoology, 
pathological classifications would never have the same significance as 
botanical and zoological taxonomies, because of the instability and muta- 
bility of pathological processes and products. Nevertheless, even patho- 
logical classifications are useful, if only in that they compel order in our 
conceptions. 

Tumours have been classified on many bases physiological, morpho- 
logical, chemical, genetical, setiological etc. ; but by far the oldest and 
most generally useful classification is that which divides them, according 
to their physiological properties, into the malignant and non-malignant, 
and for our immediate purpose this will suffice. Here, however, it must 
be noted that tumours exhibit many degrees of malignancy, both in the 
plus and minus directions. 

In former times certain intractable diseases were commonly called 
malignant, under the belief that they were due to the special influence of 
malign or evil spirits, and it is to this superstition that we owe the term 
as applied to certain tumours. 

Even at the present time it is not easy to define the precise signification 
of this much-used term, which covers a multitude of effects, although, in 



INTRODUCTORY 5 

a general way, its meaning is intelligible enough. Thus, every one under- 
stands that malignant tumours are intractable, destructive, and tend to 
a fatal end ; and these results are generally the direct consequences of their 
malignant properties. 

These comprise (1) persistence, with a tendency to softening and 
ulceration ; (2) an infiltrating mode of growth, so that the margin of the 
tumour interpenetrates and destroys the surrounding structures ; 
(3) dissemination, by which is meant the pow r er of the primary tumour to 
form secondary tumours like itself, (a) in the vicinity of the primary 
tumour, (6) in the adjacent lymph glands etc., and (c) in distant parts of 
the body, such as the liver, lungs, bones etc. ; (4) recurrence, or the 
powder of the tumour to grow again, even after the most drastic attempts 
to ensure its complete destruction by the knife, fire, caustics etc. ; and 
(5) cachexia, or a certain impairment of the general health with wasting. 

It is in the combination of these various properties, rather than in any 
one of them taken by itself, that malignancy consists, for, as Paget 
remarks : " Each may be absent in tumours having all the other features 
of malignancy, and certain of them may be seen occasionally in tumours 
which, in other respects, appear to be non-malignant." Thus cancer qua 
cancer, gives no specific indication of its presence. 

Let us consider this matter a little more in detail. 

First of all with regard to the item persistence, it can hardly be main- 
tained that the essence of malignancy lies in it, for intractability is a 
feature of all tumours, malignant and non-malignant. Moreover, many 
tumour-like swellings of granulomatous nature may be as intractable as 
cancer e.g., certain syphilitic and tuberculous lesions, mycosis fungoides, 
mycetoma, etc. 

A more characteristic feature of malignancy is infiltration, which has 
often been regarded as distinctive. Processes of the tumour substance 
interpenetrate the adjacent structures, which they destroy as it were, by 
dissolving and supplant. This mode of increase is wellnigh universal 
among malignant epithelial tumours which constitute, according to my 
estimate, 85-4 per cent, of all malignant tumours but among the sarco- 
mata it is not so general. 

In many " chronic inflammatory " processes infiltration and inter- 
penetration have been demonstrated. Thus, for the uterus, Friedlander 
and Councilman have shown that the so-called " erosions " of the os 
uteri are, in this respect, often indistinguishable from cancer ; and we are 
now acquainted with many " chronic inflammatory " lesions of the skin 
and other structures, in which the same phenomena have been noted. 

In a general way it may be said that this mode of growth is one of 
the properties, which cancer shares with immature tissues in general. 
Thus, even in the course of normal development pre-natal and post-natal 
examples of it often occur, especially in the evolution of glandular and 
papillated structures, in the conversion of cartilage into bone etc. But 
perhaps the most apposite physiological prototype of this feature of 
malignancy is to be found in placenta formation, when the epithelia of X>( 
the trophoblast and chorionic villi interpenetrate the decidual and 
maternal tissues and destroy them ; and, as we now know, when this 



6 THE NATURAL HISTORY OF CANCER 

process goes beyond certain limits a tumour results which may be either 
innocent or malignant, according to the special circumstances of the 
particular case. 

No feature of malignant disease has been more frequently regarded 
as pathognomonic than " dissemination " ; yet it is asserted that non- 
malignant tumours occasionally manifest this property, as well as certain 
pseudo-plasms of which I shall have more to say in the sequel. 

It is difficult to decide as to the validity of the claim to dissemina- 
tion which has been made for thyroid adenomata, uterine fibroids, cer- 
tain ovarian cystomata etc. No doubt many cases of this kind admit of 
being otherwise explained. Nevertheless, recent investigations of the 
changes taking place in placentation, " deportation of chorionic villi." 
" hydatid mole," and the disease called " deciduoma vel chorioma" 
seem to indicate that there is nothing specific of malignancy merely in 
" dissemination." 

The inference to be drawn from the many instances of malignant 
disease developing in the track of operation wounds, especially after the 
removal of non-malignant ovarian and uterine tumours, etc., to which I 
have specially called attention, is of similar import. 

From recent researches as to placentation it appears that, even under 
normal circumstances, cells of the trophoblast and chorionic villi con- 
stantly enter the maternal circulation during gestation, where, as a rule 
they perish ; but, under circumstances not yet determined, they may 
originate malignant or non-malignant tumours in various more or less 
remote parts of the body, such as the vagina, vulva, or even in the brain, 
lungs etc. 

There are good reasons for believing that the constituent cells of 
most malignant tumours are, in like manner, constantly entering the 
circulation, where, as a rule, they also perish and are absorbed, so that 
only those endowed with sufficient vitality to overcome this, resistance 
originate dissemination tumours. (_f ? 'v* / fo / 

To account for these phenomena, it is assumed that the circulatory 
fluids contain some substance (antitoxin, enzyme etc.) inimical to the 
intruding cells, by virtue of which their destruction is effected ; but 
when, after a time, this protective substance has become used up or so 
attenuated as to be no longer effectual, these foreign cells then originate 
tumours. It certainly accords with this view, that secondary tumours 
are seldom found during the initial stage of malignant disease. 

It is also noteworthy that certain malignant neoplasms rarely dis- 
seminate e.g., myeloid sarcoma, glioma, and " rodent ulcer " ; moreover, 
even for the same variety of malignant tumour in the same locality, the 
degree of dissemination is very variable ; and in all parts of the body 
dissemination is much influenced by the localization of the primary 
disease. These considerations indicate that the disseniinativeness of 
malignant tumours is, in a measure, conditioned by local structural and 
physiological peculiarities, which render it easy for their constituent cells 
to get access to, to live in, and to be transported by, the adjacent 
lymphatics and bloodvessels. 

Recurrence may be regarded as a consequence of dissemination, 



INTRODUCTORY 7 

chiefly of the local kind that is to say, as a continuation of the disease 
in surviving unextirpated fragments of the primary tumour or its offsets. 
Indeed, such is the great tenacity of life and the wonderful proliferative 
power, of even the most diminutive fragments of malignant tumours that, 
when any of these are left behind after operation, as is usually the case, 
they only too frequently become fresh centres of disease. 

Just as a Hydra regenerates itself after mutilation, and after it has 
been cut into small pieces, so it is with these malignant tumours. 

Viewed in this light, recurrence is, of course, no more specially dis- 
tinctive of malignancy than dissemination. 

It accords with this, that some of the most inveterate and striking 
instances of recurrence are met with among tumours not otherwise 
remarkable for their malignancy, such as rodent ulcer, myeloid and 
spindle-celled sarcomata, keloid etc. 

Moreover, non-malignant tumours sometimes grow again after 
removal, of which examples are furnished by uterine myoma, ovarian 
cystoma. mammary fibre-adenoma, subungual exostosis, condyloma, 
warts etc. ; and in macrodactyly, even after amputation of the affected 
part with the phalanges, the giant growth has been known to recur in 
the previously healthy stump ; while the recurrence, after extirpation, of 
a redundant mammary structure has lately been reported. 

The impairment of the general health cachexia that is so often 
associated with malignant tumours, never precedes the outbreak of the 
primary disease hence we infer that it is a consequence of their local 
progress. In confirmation of this it may be mentioned that cachectic 
symptoms usually disappear for a time, after the removal of the local 
disease. It is well known that the constituent cells of malignant tumours 
are remarkably prone to degenerative changes ending in disintegration. 
It seems probable that, just as dissemination depends upon the entry of 
living tumour cells into the circulation, so cachexia likewise depends upon 
the entry into the circulation of the products resulting from their dis- 
integration. These are believed to comprise toxic albuminoids, which, 
being in quantities too great to be quickly neutralized, poison the system, 
especially the blood and haematopoietic organs. 

Cachexia is more frequently seen with epithelioma than with sarcoma, 
and with some varieties of both forms of malignant disease e.g., rodent 
ulcer, spindle-celled and myeloid sarcoma it seldom occurs. Even 
among the different varieties of the same form of malignant disease, there 
are great divergencies as to the occurrence of cachexia ; thus it is much 
more frequently met with in association with cancers whose constituent 
cells are specially prone to degenerative disintegration (e.g., the ordinary 
cancer of the breast), than with those whose cellular elements are more 
stable (e.g., the lip). 

A similar condition is sometimes induced by very large non-malignant 
tumours, especially of the uterus and ovaries ; and even by some pseudo- 
plasms, such as mycosis fungoides. 

In the constitutional changes coincident with pregnancy and post- 
partuni conditions, we see manifested the physiological counterparts ot 
cachexia. 



8 THE NATURAL HISTORY OF CANCER 

It follows from the foregoing analysis of the distinctive features of 
^ malignancy, that there is nothing new or specific about them ; these effects 
may, indeed, be ascribed to the exacerbation in some directions, and to 
the diminution in others, of processes which are of normal occurrence in 
the various phases of embryonic or post-embryonic life. 
*" Thus malignancy is a relative term, of which there is no absolute 
morphological or chemical criterion. Indeed, malignancy like growth 
has no specific pathognomonic mark by which it may be certainly dis- 
X criminated and appraised ; for like growth malignancy is essentially a 
dynamic force, whose presence can only be surmised and estimated by 
careful weighing of the ensemble of the indications available for its 
diagnosis that is to say, by its effects. 

What, then, is the anatomical element upon which malignancy 
depends ? The predominant constituent of all malignant tumours is the 
cell, and it is to the cell that we must look for the answer to this question. 
Ever since the discovery of the cellular nature of the body, the cells of 
malignant tumours have been closely scrutinized, with the hope of finding 
in them some specific mark, but all in vain. The more thoroughly the 
examination has been made, the more clearly has it proved the correctness 
of J. Miiller's conclusion that : " The minutest elements of malignant 
tumours do not differ in any important respect from the constituents of 
benign tumours, nor from those of the body in its adult or embryonic 
condition." Such being the case, we can but conclude that there is no 
specific anatomical element or chemical substance characteristic of 
malignancy, other than such as occur in the physiological state. From 
this it may be inferred, that the process which manifests itself in 
malignancy, and the process of which benign tumours are the outcome, 
are the same in kind, and that they differ only in degree ; while, in the 
normal ontogeny, both have their physiological prototypes. 

In a general way, it may be said of malignant tumours, as compared 
with benign ones, that they are, structurally regarded, characterized by 
immaturity and defective organization. In their structure cells capable 
of active growth and development predominate. The morbid for- 
mation, however, always has a certain likeness to the structure of the 
part whence it originates hence malignant tumours of the same kind, 
but springing from different parts of the body, are by no means identical 
in structure. What, for instance, can be more divergent in this respect, 
than the appearances presented by microscopical sections of cancers from 
such different parts as the breast, the stomach, and the skin ? Moreover, 
if we pursue the analysis further, we shall find that even special substances 
secreted by the cells of these organs, are duly represented in the corre- 
sponding cancerous products, although the latter are never able to produce 
a perfect secretion. Thus, more than half a century ago, J. Miiller 
demonstrated the presence of casein in mammary cancers, and the special 
proneness of the constituent cells of these tumours to fatty metamorphosis 
is well known. We are thus reminded of the similar changes that the 
ells of the normal gland undergo, during the elaboration of their peculiar 
secretion. Of similar import is the cornification of the cells of cutaneous 
cancers. Waring has specially called attention to this neglected feature 



INTRODUCTORY 9 

of malignant tumours by demonstrating, that the constituent cells of 
cancers of the stomach and pancreas produce the same special ferments 
pepsin, trypsin etc. as the normal secretory cells of these organs. 

With regard to the chemical nature of malignant tumours, it is 
noticeable that albuminoid materials predominate ; and, as in actively 
growing structures in general, sugar-forming substances abound. 

The appearances revealed on microscopical examination of actively 
growing parts of malignant tumours, on the whole, have a great likeness to 
those met with during the course of the development of the affected part. 

In the case of cancers of glandular origin, the epithelial cells at the seat 
of disease become unduly numerous, and acquire a multilaminar arrange- 
ment, encroaching on the lumen of the gland, which they commonly 
obliterate. The newly formed cells, for the most part, also often lose 
their typical shape. Thus the diseased glandular structure is converted 
into a club-shaped mass of proliferating epithelial cells. Here and there 
bud-shaped collections of these proliferous cells press on the membrana 
propria, forming solid processes, which interpenetrate the adjacent 
structures in the directions of least resistance, where they branch and 
anastomose. By the repetition and further extension of this process the 
cancerous tumour is formed. In most cases these ingrowing epithelial 
columns retain their solid form ; but exceptionally they eventually 
develop more or less complete lumina, and otherwise mimic the structure 
of the gland whence they originated. 

In their entirety, the pathological appearances present striking resem- 
blance to those observed during certain stages of the normal ontogeny 
of glands, of which they may be regarded as aberrant, superinduced 
repetitions. 

Malignant tumours increase by the continuous growth and proliferation 
of their constituent cellular elements ; and the indications revealed by a 
thorough study of the minute anatomy of these cells do but strengthen 
the foregoing conclusions. Biologists have taught us the important part 
played by the nucleus, in the growth and multiplication of cells. In this 
connexion it is significant that the nuclei of the cells of malignant tumours 
are, as a rule, larger and richer in chromatin, and they more frequently 
originate mitoses, especially asymmetrical and pluripolar forms, than 
their physiological prototypes. Moreover, it has lately been shown that 
the " heterotype " mitosis, which is believed to be characteristic of gamic 
reproductive cells, is also a special feature in the multiplication of the 
cells of malignant tumours ; but of this more anon. These deviations 
from the normal are but the morphological expressions of a high degree 
of proliferative activity, which is, indeed, the essential characteristic of 
the cells of malignant tumours, and the source of all their special qualities. 
Thus the vegetative activity of cancer cells predominates over all their 
other functions ; and it is in this special dynamic quality that the essence 
of malignancy concentres. Just as cells embedded in the stroma of an 
ovarium become ova by excessive growth, at the expense of adjacent *)( 
nutritive materials, which they divert from other cells ; so we may infer 
that those cells which originate malignant neoplasms become different 
from their non-malignant congeners in a similar way. 



10 THE NATURAL HISTORY OF CANCER 



The Terms " Cancer," " Epithelioma " (vel Carcinoma), and " Sarcoma." 

At the present time the term " cancer " is used in such different 
senses, that it is necessary for those who employ it to state precisely what 
they mean by it. In the popular sense every malignant tumour is a 
" cancer " ; but in medical science the term has hitherto usually been 
restricted to certain malignant tumours viz., to those of epithelial 
origin, for which the scientific equivalent, according to the accepted system 
of nomenclature, should be epithelioma. 1 

Owing, however, to the vogue which the term cancer has obtained in 
the vernacular, as the synonym of malignant tumour, and to its employ- 
ment in this sense by the official registrars and statisticians of all modern 
communities, it seems now impossible to attach to this term any other 
significance than that sanctioned by popular usage, and this is the sense 
in which I employ it. 

We are indebted to J. Miiller for the fundamental conceptions on which 
the current nomenclature of tumours is based. He first enunciated the 
important principle, that the structural elements of every tumour have 
their analogues in the embryonic or adult tissues of the normal organism. 
In accordance with these ideas, the different kinds of tumours have been 
designated by adding the quasi-Greek radical a)^a to the name of the 
corresponding normal tissues whence they originate. 

Curiously enough, however, -in discriminating the two chief varieties 
of malignant tumours, this method has seldom been rigidly adhered to ; 
thus malignant tumours of epithelial origin have been commonly 
designated " carcinoma," and those of connective-tissue origin 
" sarcoma." 

Etymologically the former term simply means crab-like tumour 
(icap/civo?}, for which latter the Latin equivalent is cancer. The ancients 
were much struck by the crab-like aspect of these tumours, but whether 
this fancied resemblance was the outcome of superficial observation, or 
of profound study of the disease by dissection, it is not quite clear. 2 
Probably, however, they knew more of its nature and its " roots," than 
we^commonly credit them with. At any rate, the term " carcinoma " 
has persisted in scientific circles, to the exclusion of its more appropriate 
rival " epithelioma." 

In like manner the term " sarcoma " is also exceptionally derived. 
This is an ancient designation formerly applied to flesh-like tumours (adp^). 
Thus Galen says : " We call sarcoma a fleshy excrescence prceter naturam." 
There was naturally much diversity of opinion as to just what should be 
discriminated as flesh hence the term was at first vaguely used (tumores 
carnosi etc.). Prior to the discovery of the cell theory, it was commonly 

'For this conception as to the origin of the disease we are indebted to Waldeyer (1867) 
and Ihiersch, the older doctrine as to the connective-tissue origin of malignant epithelial 
tumours by metaplasia, having been generally abandoned 

Galen says : " In the breasts we often find a tumour in size and shape closely resem- 
bling the animal known as a crab, for as in the latter the limbs protrude from either side, 
so in the tumour the swollen veins radiate from its edges and give a perfect picture of 



INTRODUCTORY 11 

employed as synonymous with " fungus." Virchow is mainly responsible 
for the rehabilitation of the term, and for its modern significance. He 
described as sarcomata new formations of the connective-tissue type, 
distinguishable from the corresponding fully evolved tissues by their 
immaturity. Subsequently they were defined as tumours of embryonic 
connective tissue, or of some of the modifications that this structure 
undergoes in evolving the fully developed tissues. 



CHAPTER II 
GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 

Preliminary Apercu. 

AT the commencement of the twentieth century the great problem of 
the causation of tumours, like a gigantic sphinx, looms large on the 
medical horizon. Of this problem the genesis of cancels but a part, 
although a large one. Moreover, it is important to recollect that these 
growths are not peculiar to mankind, nor even to animals ; for, as I have 
elsewhere shown, 1 similar formations affect trees and other vegetable 
organisms. Indeed, it seems clear, as I long ago pointed out, that 
tumours may arise, under certain conditions, in any multicellular animal 
or vegetable being. 

Another important consideration is, that these abnormalities rarely 
arise in organisms living in a state of nature. It is almost exclusively 
among domesticated varieties, among those that have been kept long in 
confinement, or that have been otherwise abnormally circumstanced, 
that tumours are met with. Savages and wild animals are very rarely 
thus affected ; and it is worth noting that this comparative immunity is 
very marked throughout the whole of the monkey tribe. 

In a general way, it may be said that the animal world is much less 
prone to malignant and other tumours than humanity ; and this appears 
to me to be due to the fact that animals have been much less extensively 
subjected to the artificial influence of domestication, and to such other 
abnormal conditions of existence as I have above referred to, than man- 
kind. At any rate, it is remarkable that nearly all the examples of 
animal tumours hitherto reported, malignant and otherwise, have been 
met with in our common domesticated species ; and it is significant that 
the dog is the animal most frequently affected. 

Hitherto progress has been hindered by the want of clear conception 
as to the nature and affinities of the morbid process. Tumour formation 
has too commonly been regarded as an isolated pathological entity, having 
no connexion with other biological processes. Yet between tumour for- 
mation and morphological variation in general there is, I believe, real 
affinity ; and in ultimate analysis both may be regarded as the outcome 
of the cumulative effects of changed conditions of existence. Of these 
conditions the most important seem to me to be changed environment and 
excess of food. 

"The Principles of Cancer and Tumour Formation," London, 1888, p. 85 et seq. ; 
also "Vegetable Tumours in Relation to Bud Formation," Trans. Path. Soc. London, 
vol. xxxviii., 1887, p. 460, and ibid., vol. xl., p. 446. Vide also Chapter VI. of this work. 

12 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 13 

As I have indicated in my work on the " Principles of Cancer and 
Tumour Formation," it is my belief that factors of this kind play a leading 
part in the causation of malignant and non-malignant tumours. Now 
that the fury of the microbic prepossession has somewhat abated, it is to 
be hoped that these neglected biological factors will receive their due 
recognition. Changed food, changed habits, and changed environment 
are as potent factors in pathogenesis, when they tend in this direction, as 
they are in physiological evolution. 

Malignant tumours in mankind and animals consist mainly of albu- 
minous or proteid substances ; and it seems not unreasonable to suppose 
that they may be the outcome of excess of these substances in the body, 
and especially of such of them as serve for nuclear pabulum. When 
excessive quantities of such highly stimulating forms of nutriment are 
ingested, by beings whose cellular metabolism is defective, I believe there 
may thus be excited in those parts of the body where vital processes are 
most active, such excessive and disorderly proliferation as may eventuate 
in cancer. However this may be, I am persuaded that the ascertained 
facts justify the belief, that there is a certain relation between the con- 
ditions of existence in which alimentation plays an important part 
and the incidence of cancer. 



Some Generalities as to the Distribution of Cancer among Mankind. 

In taking a comprehensive survey of the incidence of malignant 
tumours as they affect mankind, it is important to note the wide range 
of these maladies, which are practically ubiquitous. 

Another striking feature in this connexion, is their much greater 
prevalence in some localities than in others. Careful study of these 
inequalities which although persistent are not permanent has con- 
vinced me that they are due to diversities in the conditions of existence 
of the respective populations, as I shall subsequently have occasion to 
demonstrate. 

Those who have travelled among savage peoples are practically unani- 
mous in asserting, that malignant tumours are very rarely met with under 
these circumstances ; but in most modern civilized communities diseases of 
this type are very prevalent. The reputed rarity of cancer among 
uncivilized people is fully borne out by the reports of the medical officers, 
missionaries, and other officials who have resided among such populations 
in various parts of the world, as recorded in official and other reports, to 
which I shall have to refer more in detail in the sequel. There seems to 
me to be no warrant for Dr. Bashford's contention, that the civilized 
and the savage are equally liable, and that the differences above 
indicated are merely apparent. 

To my mind it has been clearly established, that cancer is of most 
frequent occurrence among the well-to-do, highly nourished communities 
of occidental Europe ; and, within the limits of these communities, as I 
have proved, the disease is commonest among the well-to-do groups. 

Now, if I were asked to state briefly, the chief physical difference 



14 THE NATURAL HISTORY OF CANCER 

between savage and civilized man, I should unhesitatingly reply that it 
consisted in the latter being much the better nourished ; and this is the 
conclusion of most of those who have travelled among savages. The food- 
supply of the latter is, indeed, generally irregular and precarious- 
occasional gluts alternating with long spells of enforced abstinence and 
the food they get is badly cooked ; whereas the former have constantly 
available an abundance of highly nutritious and well-cooked food. 

Thus, speaking of the natives of the Gaboon region of Equatorial 
Africa, Du Chaillu says : " No wonder they are so fond of meat : they have 
it so seldom i.e., only when they can get it by hunting." 

From indications of this kind, it may be inferred that nutrition and 
alimentation play an important part in cancer causation, as I shall 
subsequently have occasion to demonstrate more in detail. 

It has been noted in the United States, in Australia, and in some other 
communities, that immigrants are very much more liable to malignant 
disease than are the native-born population ; and that they experience in 
their new homes higher cancer death-rates than prevail in their native 
countries. Hence it may be inferred, as I shall indicate more fully in 
the sequel, that abrupt change of environment may also be a factor in 
the causation of this disease. 

Race, Complexion, and Conditions of Existence. 

In human beings, well-marked constitutional peculiarities and morbid 
proclivities, are often reputed to be correlated with race and complexion. 
I now propose to inquire whether the incidence of cancer is influenced by 
factors of this kind. 

So far as present indications go, it appears that all racial varieties of 
mankind are liable to malignant tumours ; but I am not aware of any 
really satisfactory data, as to the relative incidence of the disease among 
the different races. From such information as is available, I have come 
to the conclusion that ethnological factors per se are of far less importance 
in determining the incidence of cancer, than are the conditions of existence 
to which the race has been exposed. I have arrived at this conclusion 
mainly from studying the incidence of the disease, as it has affected such 
well-marked racial types as negroes, North American Indians, and Jews. 

In their native African homes, the ancestors of the negro slaves of 
the United States like other similarly situated savages are believed to 
have been almost exempt from malignant tumours. Most of the early 
writers testify as to this' comparative immunity, which is in entire accord 
with what we now know as to the present condition of the kindred tribes 
in Africa, among whom cancer is very rare, as I shall subsequently have 
occasion to indicate in detail. 

Now, in Du Chaillu' s interesting " Travels in Equatorial Africa," we 
have an admirable account of the modus vivendi of these tribes, before 
contact with Europeans, to the salient features of which I have previously 
alluded as determining this immunity. 

Transplanted to the United States, and having lived there in slavery 
for over two centuries, these negroes were then found by the United States 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 15 

authorities to have acquired greatly increased liability to cancer, to 
which, however, they were very much less prone than their white masters. 
Thus, Chisholm's statistics show that, before the emancipation, the whites 
were more than twice as liable as the blacks, and this was specially 
noticeable with regard to uterine cancer. The regimen under which they 
lived during this period, has been well described by Dr. S. Harris l as 
follows : The planters gave their slaves the best hygienic surroundings 
possible ; they had plenty of simple, nutritious, and well-prepared food, 
and enough out-of-door labour ; sleep and recreation were well regulated 
and sufficient ; they were \vell clothed, forced to keep clean, comfortably 
housed, and well cared for in sickness. The defective and unhealthy were 
debarred from reproduction, in which the healthy and able-bodied were 
encouraged ; in short, everything was done to promote health, vigour, and 
long life ; and under this system the slaves multiplied, and had splendid 
health better, in fact, than that of their white masters. Thus, the 
Charleston statistics, from 1822 to the outbreak of the Civil War, show 
that the general death-rate for whites was 25-98 per 1,000 living, while 
that for blacks was only 24-04, and throughout the South similar con- 
ditions prevailed. 

After thirty-five years of freedom, the negroes' health is found to have 
markedly deteriorated ; they now experience an increased general mor- 
tality, with greater proclivity to nearly all kinds of disease, especially to . 
tubercle, pneumonia, etc. Even their reputed comparative immunity 
from malaria has been lost, for the negro death-rate from this cause now 
greatly exceeds that of the whites. Everywhere, at all ages and in both 
sexes, these negroes now have greater mortality and morbility than their 
white compatriots ; and they have become a short-lived race. Thus, the 
Charleston data show that from 1865 to 1894 (i.e., after emancipation) 
the negro general death-rate per 1,000 was 43-29, against only 22-7 for 
the whites. 2 

During the emancipation period, the proclivity to malignant tumours 
greatly increased among negroes, the mortality returns for 1900, showing 
a death-rate from this cause of 48 per 100,000 living, as against 66-7 for 
whites. 3 The Louisville City Hospital reports, and the data collected by 
Matas for New Orleans, which there are good reasons for regarding as 
more reliable, in reference to this particular, than the national statistics, 
show that malignant tumours are now as common there in negroes as in 
whites (Rodman). With regard to uterine cancer, negresses are now 
more prone to it than their white sisters, the respective death-rates for 
1900, being 20 for blacks and only 15-7 for whites. 

Mammary cancer is also now nearly as common in negresses as in 
white women, the respective death-rates for 1900, being 7-9 for the former 
and 9-1 for the latter. Thus, from a condition of comparative immunity, 
these negroes have now become nearly as prone to malignant tumours as 

1 American Medicine, September 7, 1901, p. 375. 

2 The Twelfth United States Census Report for 1900, gives the death-rates for 
negroes and whites, as 31 '8 and 17 '3 respectively. 

3 The corresponding figures for 1890 are blacks 36'65, whites 53'93 ; and, for 1880, 
blacks 12-17, whites 27'96. 




16 THE NATURAL HISTORY OF CANCER 

their white neighbours. This result I ascribe to sudden, violent alteration 
in their mode of life, with its predominant gluttony and laziness. 

In like manner, the North American Indians are believed to have been 
almost exempt from cancer in their primitive savage condition ; but, with 
the altered mode of life consequent on contact with modern civilization, 
this comparative immunity has now to a large extent passed away, 
although they are still less prone to malignant tumours than their white 
compatriots. 

In this connexion it should be borne in mind, that in their primitive 
condition these savages had no horses and no firearms ; consequently it 
was no easy matter for them to kill the fleet buffaloes, on which they 
mainly depended for subsistence ; hence, in their primitive condition, 
they were generally less well nourished than when, after contact with 
whites, they had, by the acquirement of horses and firearms, become 
assured of a constant supply of their favourite food. 

In comparatively recent times much valuable information has been 
forthcoming as to the incidence of disease among Jews, the general 
outcome of which is to show that this race has a low death-rate, and more 
than average longevity. 

Jews suffer less than most races from tuberculous disease (especially 
phthisis), pneumonia, alcoholism, diarrhoeal affections, and some other 
maladies ; but they are more prone to diseases of the nervous system, 
especially to diabetes and insanity. N. 

The Jewish race being widely scattered throughout the world, and the 
conditions of existence of its various communities being exceedingly 
diverse, is admirably circumstanced for illustrating the comparative 
importance of race factors versus conditions of existence, in determining 
the incidence of cancer. Unfortunately, although the comparative 
pathology of the Jew has been fully worked out for most diseases, with 
regard to malignant tumours, the data are scanty, and leave much to be 
desired. On the whole, however, the available indications point clearly 
to the conclusion, that the liability of Jews to cancer varies with their 
mode of life, approximating to that of the people among whom they dwell, 
but generally being somewhat inferior to it. It has often been asserted 
that persons of the Jewish race are very rarely affected, but this is evi- 
dently a mistake. In the United States J. S. Billings 1 found, that the 
Jewish cancer mortality was about the same as that for the rest of the 
white population. He gives the cancer mortality per 1,000 deaths as 
follows : 

Jews. Other U.S. Whites. 

Males 13-58 .. .. 13'09 

Females 21'65 . . . . 23'59 

Billroth's experience in Vienna was somewhat similar. 

Dr. B. W. Richardson, who had considerable experience among the 
wealthy Jews of West London, found that they were as prone to malignant 
tumours as other well-to-do people of this part of the metropolis. Referring 
to the alleged great rarity of this disease among Jews, he says : 2 " I 

1 *enth United States Census Report for 1880. 

2 Asclepiad, vol. viii., 1891, p. 145. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 17 

regret to be obliged to state from personal knowledge, that the Jewish 
community is by no means exempt from cancer. There is no difference 
in the character of the affection in the Jew, nor any selection of sex, nor 
any organic selection. With the Jews, as with persons of other races, 
women are most liable to cancer, but I have witnessed the malady in 
both sexes. I have known Jewish women who have died of uterine 
cancer, and of cancer of the breast. My own experience is amply 
sufficient to disprove the rash assertion of Jewish racial exemption." 

An anonymous medical man, who has practised for twenty-five years 
among London Jews, recently wrote 1 as follows : " There is undoubtedly 
an impression in the minds of the members of the Jewish community 
that, far from being exempt, the Jews are especially prone to suffer from 
malignant growths ; and I must admit that I have been somewhat inclined 
to share this view, although it has sometimes appeared to me that cancer 
is less prevalent now among them than it was in my earlier experience." 

He then gives some statistical data based upon the burial returns of 
the United Synagogues of London, which for the year 1900, show that 
2-3 per cent. 2 of the deaths were stated to be due to cancer, or about 
one-half the ratio for England and Wales in general. 

Comparing this result with the outcome of his own experience, he 
says : " It is impossible that there is not some fallacy underlying this 
immense discrepancy " ; and he thinks that the explanation of this 
fallacy is to be found, in the comparatively large number of children and 
young adults believed to be comprised in the Jewish population, as to 
which, however, there is no clear evidence. 

It appears to me that the author of this instructive communication 
has failed to find the fallacy, which he believes underlies his statistics. 
It is hardly likely that such diversities in age distribution as he refers to, 
will account for such considerable disparities as his data show. 

The really important part of the fallacy seems to me to consist in 
this : that unlike things have been compared together. The great bulk 
of the London Jewish population, whence these data are derived, is an 
East-End population, living under conditions of stress and hardship ; 
whereas the average Britisher is a comparatively prosperous and well- 
to-do being. To get a correct idea of the relative incidence of this disease 
among Jews and non-Jews, only populations that are, roughly speaking, 
similarly conditioned should be compared. We see the necessity for this 
in the fact, that the cancer mortality of West London is so much higher 
than that of the East End ; and this was the case before the present Jewish 
immigration, when the respective populations consisted almost entirely 
of Britishers. For instance, during the decennium 1881-1890, the cancer 
mortality of Stepney was only 3-7 per 10,000 living, as against 5-8 for all 
England ; and at still earlier periods and in other localities, the same 
disparity is apparent. Even when correction has been made for age and 
sex distribution, and for deaths in public institutions, this disparity still 
remains ; indeed, in the poorest parts of all our large towns, the cancer 

1 British Medical Journal, vol. i., 1902, p. 681 ; also ibid., vol. ii., 1905, p. 734. 

2 Estimated to be equivalent to a death-rate of 5'2 per 1,000 living, as against 9'5 for 
London in general (1899). 

2 



18 THE NATURAL HISTORY OF CANCER 

mortality is always much below the average. Further, in Jewish quarters 
in London, whether rich or poor, as among non-Jews, the cancer mortality 
is steadily increasing. 

I am indebted to the kind intervention of Dr. F. L. Hoffman, the well- 
known statistician of the Prudential Insurance Company of America, 
for the following note on this subject by Dr. M. Fishberg of New York, 
who has specially studied this subject from the American standpoint. 
He says : * "It appears from all the available data that cancer is by no 
means rare among Jews, although it is less frequently met with than 
among non-Jews. This latter condition I explain as due to the fact that 
cancer of the uterus and female breast is comparatively rare among Jews ; 
and, as is well knowTi, the two last-mentioned organs are the very ones 
most frequently affected in non-Jews. On the other hand, cancer of the 
gastro-intestinal tract is very frequent among Jews ; thus, nearly 45 per 
cent, of all cases of malignant disease in Jews occurred in the stomach, 
intestines, liver, pancreas, rectum etc., while among non-Jews only 23 per 
cent, of the patients were affected with cancer of these organs. Another 
point is, that sarcoma is more frequently met with in Jews than in 
Gentiles." 

With regard to these interesting remarks, my own impression is that 
it has not yet been proved that Jewesses have any special immunity from 
uterine and mammary cancer ; while, as to the gastro-intestinal mani- 
festations of the disease, I have found, as I shall subsequently have to 
indicate in detail, that more than half of all cancers in Britishers have 
this localization. 

As tending to confirm the belief that Jews generally experience a 
some\vhat lower cancer mortality than their non-Jewish compatriots, 
reference may be made to an instructive publication by Dr. F. L. 
Hoffman, 2 in which it is shown that in the United States those of Polish 
extraction who are mostly Jews have a lower death-rate from cancer 
and tumour, than any other national group in this now composite 
community. 

In illustration of his remarks, he cites the following data, showing 
the comparative mortality from these diseases of the various nationalities 
per 100,000 of population : 



Aires. 


Native-born 
United States 
Whites. 


Polish 
(mostly Jews). 


German. Irish. 


Italian. 


45 to 64 . . I 
65 and upwards 


155-3 
374-9 


92-3 
263-5 


238-6 232-2 
561-5 479-9 


119-4 

392-7 



Dr. W. A. King, the chief statistician of the Twelfth United States 
Census Report, referring to this subject, says : 3 " The death-rates per 

"Jewish Encyclopaedia," vol. iii., p. 529, New York, 1902: to which, however, I 
have not had access. 

" Race and Mortality," New York Examiner, October, 1902, p. 635. 
Twelfth United States Census Report for 1900, vol. iii., part i. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 19 

100,000 of white population, show that the mortality due to malignant 
tumours was highest among those whose mothers were born in France 
(92-8), in Scotland (81-8), and in Germany (78-2) ; and lowest among 
those whose mothers were born in Russia and Poland (25-7), in Italy 
(22-8), and in Hungary and Bohemia (31-5). The rate was lower among 
those whose mothers were born in the United States (48-3), than among 
those whose mothers were born in Ireland (76-4), or in England and 
Wales (72-0)." 

Here, again, it will be noticed that those of Russian and Polish extrac- 
tion, who are mainly of Jewish race, have a comparatively low cancer 
mortality. 

In this connexion, however, it must be remembered that these people 
are among the poorest in the United States ; and the Italians, who share 
their poverty, also share their comparative immunity from cancer. 

The lowest cancer death-rates in Austria are met with among the 
Poles of Galicia and Bukowina, who are largely of Jewish origin ; and in 
the Prussian provinces bordering on Poland, where considerable numbers 
of Jews are met with, exceptionally low cancer death-rates prevail. 

The idea that the eating of pork, per se, has anything to do with 
variations in the incidence of the cancer mortality may certainly be 
dismissed. From data bearing on this subject, collected by Bauby 1 in 
the neighbourhood of Toulouse, it is shown that those who eat pork are 
no more liable to cancer, than those who partake of other kinds of flesh 
food. 

The anonymous correspondent to whose publication I have previously 
referred, also comes to this conclusion. He says : " At the present time 
a considerable number of London Jews are by no means strict adherents 
to the dietary laws, and it will be within the experience of every one who 
has practised among them, that cancer attacks the orthodox in this 
respect, as it does the heterodox." 

As a general rule, I think it will be found that the Jewish cancer 
mortality has very little to do with race or with racial customs per se ; 
but that it varies, according to the conditions of existence, in different 
localities and countries. 

It should, however, be borne in mind that the Jewish race is of oriental 
origin ; and even now Jews retain something of the oriental heritage of 
abstemiousness in flesh-feeding, as compared with the grossness in this 
respect of most of their occidental compatriots. 

Many similar facts might be adduced, showing the tendency of the 
cancer mortality to vary in accordance with the mode of life of individuals, 
rather than with inherent racial peculiarities. 

The United States census reports for several decades, as previously 
mentioned, have furnished data showing the comparative cancer mortality 
of each of the chief racial factors contributing to its composite popula- 
tion. These records show remarkable differences between the cancer 
proclivity of American-born persons, and those whose mothers were born 
in some other country. Lyon 2 found that the cancer mortality of the 

1 Bulktin Med., October 14, 1894. 

2 American Journ. Med. Science, vol. xxviii., 1901, p. 640. 

22 



20 THE NATURAL HISTORY OF CANCER 

foreign-born inhabitants of the city of Buffalo (1880 to 1899) was more 
than 4i times greater, than that of the American-born inhabitants. In 
Australia and New Zealand similar occurrences have been noted, as I 
shall subsequently have occasion to indicate. Of like import is the 
converse fact, that persons of British descent who have been settled for 
some generations in the United States, Australia, and New Zealand, then 
experience a much lower cancer mortality than is prevalent in their 
original homes. 

Dr. J. Beddoe l has called attention to the further fact, that although 
cancer is very prevalent in Norway and Sweden 2 among one of the 
blondest populations in the world, comprising less than 5 per cent, of 
the dark type it is of the greatest rarity in Iceland and the Faroe Islands, 
which are inhabited by persons of the same race as the Norwegians. 

According to Panum, who wrote more than a quarter of a century 
ago, cancer was then almost unknown in the Faroe Isles ; and in Iceland 
it was exceedingly rare, the death-rate from this cause then being only 
7 per 100,000 (Hirst). 

Dr. R. Jeaffreson, who visited these islands in 1892, informed me 
that cancer was then very rare there. During some months' residence in 
the Faroe Isles he never saw a single case, but the resident doctors told 
him that they occasionally met with an instance generally in half- 
breeds or Danish immigrants. In Iceland he found that cancer was as 
exceptional as in the Faroes. According to Dr. Lazarus-Barlow, 3 how- 
ever, the disease has much increased of late, the cancer death-rate for 
1900, being estimated at 28-8 per 100,000. 

In 1890, there were only two deaths from cancer in the whole of 
Iceland ; but in 1900, twenty-two of such deaths were notified. 

In Greenland, according to Panum, malignant tumours are of great 
rarity. 

All these facts, which might easily be multiplied, point clearly to the 
conclusion, that it is neither race nor complexion alone, but rather 
diversity in the conditions of existence, which determines the incidence 
of this malady. 

The Scandinavian and North European populations are mainly 
blonde, and they have a very high cancer mortality. The Italians and 
South Europeans are predominantly dark (70 per cent.), and their cancer 
mortality is much below the average. 

In this country, however, I have convinced myself that the majority 
of cancer patients are of the dark type ; and it is to the female sex that 
this preponderance is chiefly due. Thus, of 256 female cancer patients 
examined by me, 150 were of dark and 106 of fair type. In order to 
appreciate the significance of these results, it must be borne in mind 
that among the London lower classes, whence these patients were derived, 
the fair type decidedly predominates, Dr. Beddoe's estimate being 57 per 
cent, of the latter, to 43 per cent, of the former.* On this basis, I calculate 

1 Allbutt's " System of Medicine," vol. i., 1896, p. 35. 

In 1900 the cancer death-rate per 100,000 inhabitants was 92. 

Arch. Middlesex Hosp., vol. v., 1905 p 275 
4 " The Races of Britain," 1885. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 21 

that malignant tumours are more than twice as frequent in dark as in 
fair-complexioned individuals. Here mention may be made of the 
curious fact that I have never met with, and cannot cite, a single instance 
of, malignant disease in an albino. 

In this connexion it may also be noted, that the stress of life in large 
towns seems to exert a much more injurious influence on the fair-com- 
plexioned, especially in early life, than on those of darker hue. Owing 
to this cause, it is believed that fair-complexioned types are gradually 
being supplanted in our large towns. Changes of this kind, which are 
very subtle and far-reaching, may be among the factors contributing to 
the increased cancer mortality of modern times. 

Finally, it may be here mentioned that among the natives of India, 
Egypt, Algeria, Australia, New Zealand, South Africa, Canada * etc., 
malignant tumours are extremely rare ; whereas, among the white people 
settled in these localities, tumours of this kind are comparatively common. 
Taken in conjunction with the foregoing considerations, this indication 
evidently points to something in the mode of living, as being the deter- 
mining aetiological factor in cancer genesis. ' 



General Survey of the World-wide Distribution of Cancer. 

In every part of the world the incidence of cancer presents many 
variations. Thus, it is much more prevalent in some countries than in 
others ; and within the limits of particular communities even in the 
smallest administrative areas variations of this kind are everywhere 
noticeable. 

I have previously pointed out the much greater frequency of the 
disease in civilized than in savage communities. 

As a general rule, malignant tumours are of much commoner occur- 
rence in temperate and cold, than in tropical or hot regions. 

The Danish Government report that cancer is not unknown, even in 
the Arctic .regions ; but no definite information is available as to its 
incidence. As we get to know more about remote localities, it will 
probably be found that no settled community is really exempt. 

Although it is improbable that any tropical community is really 
immune from malignant tumours, I am convinced that this type of 
disease is of very much rarer occurrence among tropical people, than 
among the inhabitants of the temperate regions, and especially those of 
occidental Europe. 

I shall subsequently adduce abundant evidence from many parts of 
the world, as to the correctness of this conclusion. Here I can only offer 
a few remarks on the general aspect of the question. At the outset, it 
must be mentioned that, with the exception of India and Brazil, all the 
chief centres of civilization are situated in the temperate or extra-tropical 
regions e.g., Europe, China, Japan, United States, British North 
America, Australia, New Zealand, Cape Colony etc. 

In Europe, cancer is very much more prevalent than in any of the 

1 Formerly also among the Redskins now nearly extinct of the United States. 



22 THE NATURAL HISTORY OF CANCER 

great divisions of the world ; indeed, it is probable that, with the excep- 
tion of China, more deaths occur from this cause in Europe and the United 
States, than in all the rest of the world together. Moreover, it is notice- 
able that the lowest European cancer death-rates are found along its 
extreme southern fringe i.e., the shores of the Mediterranean, 1 com- 
prising the Spanish, Italian, Austrian, Turkish, and Grecian littorals, as 
well as the adjacent islands (Sardinia, Sicily, Corsica etc.). 

Although we have no statistical data as to the prevalence of cancer 
in Asia, at all comparable with the comprehensive reports issued by most 
European Governments, yet, from such information as is available, it is 
evident that this disease is of much commoner occurrence in the great 
extra-tropical empires of China and Japan, than it is in the essentially 
tropical community of India. With regard to Northern Asia, no informa- 
tion is at present available. 

In Australasia cancer is everywhere fairly common among those of 
white descent, who are congregated in the extra-tropical regions ; but, 
among the aborigines, it is so rare as to be almost unknown. 

It seems perfectly clear that malignant tumours are of much rarer 
occurrence in Africa, than in any other of the great divisions of the world ; 
and most of this vast continent is tropical, with the exception of Cape 
Colony and its vicinity. It is only in this extra-tropical region that 
cancer is at all common ; and even here, it is those of white descent who 
are the chief sufferers, for the natives are seldom affected. 

In the American Continent cancer is much more frequent in its northern 
or temperate part than elsewhere. Thus, this malady is common in all 
parts of British North America, except among the aborigines. It is the 
same in the United States, where, moreover, the cancer mortality of the 
Northern States is more than double that of the Southern ones. 

In Mexico and the Central American communities, cancer is decidedly 
rarer than in the United States. According to Jourdanet, it is almost 
unknown in the hot regions of Mexico ; whereas in the cool regions, on 
the high plateaux, it is frequent. 

In the tropical regions of South America, of which Brazil is the great 
exemplar, cancer is rarer than in any other part of the American Continent; 
and in Brazil, according to Sodre, the malady is rarest in the equatorial 
regions, increasing in frequency with remoteness from the equator. It 
accords with this, that cancer is much more frequent in the Argentine 
Republic and in Uruguay, than in Brazil. 

How is the much greater prevalence of malignant tumours in tem- 
perate than in hot climates, which this world- wide survey reveals to be 
accounted for? Races, says Hippocrates, "are the daughters of 
climates"; but, as I have previously shown, diversities of this kind 
cannot be explained by racial peculiarities. The influence of climate 
per se, is as impotent as race per se, to solve this problem. Thus, it is 
only in the conditions of existence, that an adequate solution can be 



uoitdTv^n! t ? < P eni . ker> the Mediterranean littoral-from Gibraltar to the Tiber-is 

SSttSttSttSStettZttTE^ 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 23 

found ; and in this connexion climate is no doubt a powerful factor. Thus 
regarded, the greater variability of the temperate as compared with the 
tropical climates, is probably quite as important as the lower average 
range of temperature. The greater bulk, muscularity, activity, and 
superior physical endowment of the people of temperate climates, as 
compared with 'their tropical counterparts, may be mainly ascribed to 
the former cause, which favours more active tissue changes ; and so 
creates the desire for a highly stimulating and nutritious diet, which 
finds its expressions in a predominantly carnivorous alimentation. On 
the other hand, tropical people, with their less variable climates, are 
remarkable for their extreme frugality in living, their open-air existence, 
and their predominantly vegetarian diet. It is a remarkable fact, but 
nearly all tropical people manifest decided aversion for a too carnivorous 
diet ; and this cannot be ascribed to backward civilization, but it is rather 
due to recognition of the fact, that much animal food, in hot climates, 
predisposes to ill-health and disease. The great precocity of growth and 
development in tropical populations, with the correlated premature 
senility, the high general and infantile mortality which greatly exceeds 
that of Europe, often to the extent of being more than double and the 
consequent short duration of life : all of these effects are probably chiefly 
consequent on a high range of temperature ; while to this factor may 
also be ascribed the early sexual maturity, and the great reproductive 
activity which is so noticeable. 

Such is the direction in which, as it seems to me, the answer to our 
question must be sought. 

" How vast," says Sir R. Giffen, " must be the economic gulf separat- 
ing the people of Great Britain from India and like parts of the Empire, 
when we find that 42,000,000 of people in the United Kingdom consumed 7< 
in food and drink alone, an amount equal to the whole income of over 
300,000,000 of people in India." 

In the same strain Meredith Townsend, one of the latest and best 
exponents of Indian life, writes : " There is no abstemiousness in the 
world, and no thrift, like the thrift and the abstemiousness of the average 
native of India. . . . Millions of men in India, especially on the richer 
soils and in the rice deltas, live, marry, and rear healthy children upon 
an income which, even when the wife works, is rarely above two shillings 
a week, and frequentty sinks to eighteenpence." 

The natives of India live on millet or rice, a little milk, with the 
butter from the milk, and the vegetables they grow ; and of these they 
partake sparingly. They seldom eat any meat. It is only the Brahmins, 
the priestly caste, who form but a small fraction of the immense Hindoo 
population, who never eat any flesh food. The immense majority of the 
people live a rural life, depending upon agriculture for their subsistence. 
Such are the conditions of existence in India ; and India is typical of the 
tropics. 

Now contrast the tropical mode of living with that prevalent in our 
country, where all the conditions are so different ; where the average wage 
of the worker amounts to thirty-eight shillings a week ; and where the 
alimentation comprises a meat consumption of over 130 pounds per head 



24 THE NATURAL HISTORY OF CANCER 

per year, together with an abundance of other highly nutritive proteid 
food products, fats etc. 

Moreover, it is in the tropics that the human race is believed to have 
originated, and there the anthropoid apes, our nearest animal connexions, 
who are mainly vegetarians, still flourish ; and are seldom, if ever, affected 
with malignant tumours. 

It is to conditions such as these and their consequences, as I shall 
often have occasion to point out in the sequel, that the greater prevalence 
of malignant tumours in temperate, than in tropical countries, must be 
ascribed. 

Unlike certain specific infective diseases, such as malaria, with which 
cancer has often been compared, this malady is not limited to definite 
localities, but is practically ubiquitous. Ubiquity differentiates cancer 
from all parasitic maladies, for even tubercle is far less ubiquitous than 
cancer. Cancer and tubercle centre in temperate climates, whereas 
malaria is the predominant malady of the tropics. 

Tumours including the malignant kinds seem to me to be more 
akin to malformations per excessum, than to specific endemic maladies. 
The congenital origin of many tumours, malignant and otherwise, testifies 
against their parasitic origin. Malformations and other morphological 
variations, like tumours, are found in all localities, climates, and races ; 
and it is specially noticeable that, like tumours, they are much commoner 
in civilized humanity than in savages ; and in domesticated animals, 
as well as in those that have been kept long in confinement, than in 
animals accustomed to a less artificial environment. Here it may be 
mentioned, that the prevalence of defects of this kind has greatly 
increased in our country during the last half-century. 



General Survey of the Distribution of Cancer in Europe. 

Statistical records show that malignant tumours are very much more 
prevalent in Europe, than in any other of the great divisions of the world ; 
and it is specially in the northern and central parts of this Continent that 
the cancer mortality is so terribly high. In Southern Europe the inci- 
dence of the disease is much less, and I have previously referred to its 
special rarity along the Mediterranean littoral. 

Although the official reports of different countries are, in some respects, 
not always strictly comparable, yet the following data may be taken as 
giving a fairly accurate notion as to the comparative incidence of the 
disease. The figures show the cancer death-rates per 100,000 living for 
the year 1900, unless otherwise stated. 

The maximum incidence of the disease seems to be in Switzerland, 
where, according to Nencki, the cancer death-rate for the year 1898 was 
132, and for the decennium 1895-1904 it has been estimated at 128. 

In Denmark the malady appears to be nearly as rampant as in Switzer- 
land, for the cancer death-rate for all the towns, for the years 1892-1897 
averaged 130. 

France comes next with a cancer death-rate of 104, for all towns of 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 25 

above 3,000 inhabitants ; 1 and is closely followed by Sweden, with a 
cancer mortality of 102 for its town population. 

The figures for the other countries are as follows : Holland, 93 ; 
Norway, 92 ; England and Wales, 82 ; Scotland, 80 ; Germany, 71 
(Prussia, 59 ; Bavaria, 98 ; Baden, 101 ; Saxony, 95 ; Wurtemburg, 93) ; 
Austria* 70 ; Ireland, 61 ; Italy, 52 ; Spain, 39 ; Belgium, 36 (1880-1887) ; 
and Hungary, 33. 

As to Russia, no satisfactory data are available, but the disease seems 
to be everywhere fairly prevalent. 

In Greece, Turkey, and the Balkan countries, cancer is believed to be 
rare, but hardly any recent information is available ; 2 and with regard to 
Portugal it is the same. 

Along the Mediterranean littoral, as previously mentioned, some of 
the lowest cancer death-rates in Europe are to be found. Thus, on the 
Spanish coast, the figure for the province of Almeira is 25, that for 
Valencia 28, for Genoa the same, for Alicante 29, while the figures for 
Andalusia and Catalonia are equally low. Among the natives at 
Gibraltar the cancer death-rate is 25, and at Malta the disease is 
reported to be very rare among the natives. 3 On the French coast, 
the cancer-mortality is everywhere much below the French average ; 
but precise data are only available for the towns, and of these Marseilles 
has the lowest cancer death-rate of any large town in France viz., 69. 
In Corsica the disease is very rare, the figures for the chief towns being 
32 (1895). In Sardinia the cancer death-rate is only 19, and in Sicily 
34. On the Italian coast the figure for Calabria, for Basilicata, and for 
Apulia is 30, and for Abruzzie Molise 35. On the Austrian littoral, the 
cancer death-rate for Croatia is 16, and for Dalmatia 19. 

An examination of this list shows, that malignant tumours are of most 
frequent occurrence in those communities where the inhabitants are pre- 
dominantly well-to-do ; and where they now are, and for some time have 
been, exceptionally well nourished. At first sight, it might be thought 
that such a description hardly applies to the countries at the head of my 
list, for the aggregate wealth of Switzerland and the Scandinavian 
countries is comparatively inconsiderable. It must, however, be borne 
in mind that these communities have no paupers and no millionaires ; 
and a careful examination of the subject reveals the fact that their 
average of well-being is higher than elsewhere in Europe, as is indicated 
by their exceptionally low general, infantile, and tuberculous death- 
rates. In fact, vital statistics show that the inhabitants of these countries 
are, on the average, the healthiest and best-nourished people in Europe. 

Very different conditions of existence prevail where the lowest cancer 
death-rates are found. Here the people are predominantly poor, of 
necessity very frugal, subsisting on an alimentation which comprises but 
little proteid food ; and these conditions are chronic. 

The attempt to explain these diversities as due to inequalities in the 

1 Comprising only about one-third of the entire population. 

2 For Servia (1895 to 1904) the cancer death-rate has been estimated at 8 per 100,000 
living ; the phthisis death-rate being 245. 

3 Boudin states that 3,200 deaths among the indigenes (1822-34) comprised not 
a single cancer death. 



20 



THE NATURAL HISTORY OF CANCER 



age and sex distribution of the respective populations has completely 
failed, wherever the requisite data for making such corrections have been 
available ; and, primd facie, it is obvious that such diversities as those 
above indicated, are far too marked to be explained in this way. 

Here it may be noted that the people of Europe now are, and for a 
long time have been, on the average, better nourished than those* of any 
of the other great divisions of the world. 

In plenty the Hydra buds, in less favourable circumstances it repro- 
duces sexually. Mankind, under similar circumstances, as I have indi- 
cated in my work on the " Principles of Cancer and Tumour Formation," 
is apt to be affected in an analogous way. Here the gemmation manifests 
itself as tumour formation, which may be regarded as reversion from 
dominant sexuality, to a more or less incomplete attempt at agamogenesis. 
In ultimate analysis, then, both gemmation and tumour formation may 
be ascribed to what Geddes calls predominant anabolism. The more 
thoroughly the cancer problem is studied in its ensemble, the more manifest 
this inter-relation becomes. 

The following remarkable data by Bertillon, showing the comparative 
fertility of the well nourished and of the poorly nourished, is of much 
interest in this connexion : 

TABLE SHOWING BIRTHS PER 1,000 WOMEN AGED 15 TO 50 PER ANNUM, 
IN DIFFERENT QUARTERS OF LONDON, PARIS, BERLIN, AND VIENNA. 



Classes of Population. 


Average. 


London. 


Paris. 


Berlin. 1 Vienna. 


Very poor 


153 


147 


108 


157 200 


Poor 


132 


140 


95 


129 164 


Comfortable .. ... j 112 


107 


72 


114 155 


Very comfortable 
Rich 


105 

78 


107 

87 


65 
53 


96 153 
63 107 


Very rich 


51 


63 


34 


47 71 



This antagonism between individuation and reproduction long ago 
secured recognition in the homely adage, " The rich for luck, and the 
poor for children "; and in this connexion Adam Smith called attention 
to the poor half-starved Highland crofter women, with their families of 
twenty or more children. 

I shall often have occasion to refer to these fundamental etiological 
conceptions in the sequel, but for the present these brief introductory 
remarks must suffice. 

It accords with the foregoing that the cancer mortality of the capital 
cities and great towns, where the wealth of the nations is clotted, is 
generally above the average ; while in rural districts the disease is less 
prevalent than in towns, although there are here some exceptions. There 
can be no doubt that the town people, owing to their greater earning 
capacity, are, as a rule, better nourished than the rural inhabitants ; 
although the great inequalities in the distribution of wealth, which are 
specially prevalent in urban communities, with their paupers and mil- 
lionaires, often neutralize this effect. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 27 

The cancer death-rates for the chief European capitals for 1900, were 
as follows : Copenhagen, 139 ; Stuttgart, 127 ; Dresden, 125 ; Vienna,* 
121 ; Munich, 119 ; Edinburgh, 116 ; Stockholm, 110 ; Berlin, 109 ; 
Paris, 105 ; Berne, 105 (with canton) ; St. Petersburg, 100 ; Amsterdam, 
98 ; London, 96 ; Dublin, 93 (with county) ; Prague, 85 ; Madrid, 78 ; 
Rome, 77 ; Buda-Pest, 72 ; Ghristiania, 2 66 ; and Brussels, 44. 

In Constantinople, Athens, and the capitals of the Balkan States, the 
disease is said to be comparatively infrequent, but no recent data are 
available. 

For the chief European towns the corresponding rates are as under : 

Geneva, 177 ; Rouen, 173 ; Lyons, 153 ; Florence, 137 ; Reims, 132 
(1895) ; Danzig, 122 (1895) ; Ravenna, 120 (1887-1899) ; Strassburg, 118 ; 
Keil, 113 ; HaUe, 112 ; chief Danish towns, 111 ; Breslau, 109 ; Dundee, 
107 ; Venice, 103 ; Milan, 101 ; Trondhjem, 99 ; Utrecht, 97 ; Hamburg, 
97 (1898) ; Bordeaux, 97 ; Aberdeen, 95 ; Cologne, 91 ; Hague, 90 ; Rotter- 
dam, 90 ; Birmingham, 85 ; Seville, 85 ; Glasgow, 82 ; Bremen, 81 (1875- 
1878) ; Malmo, 80 ; Manchester, 78 ; Liverpool, 77 ; Marseilles, 69 ; 
Dusseldorf, 61 ; Genoa, 59 (1887-1899) ; Turin, 59 (1,887-1899) ; Naples, 
56 (1899) ; Barcelona, 53 ; Valencia, 39 etc. 

Some of the highest cancer death-rates known to me have been met 
with in small villages of Normandy viz., Oulchy, 400 ; St. Sylvestre, 8 
363 (1880-1887) ; Rocroi, 266 ; and Cormeilles, 203. In this part of 
Normandy cancer is more prevalent than in any other district of France 
viz., for the departments of Eure et Loire 167, and for 1'Aisne 161 
(1900). A very high cancer mortality is also reported at Cracow, 316 
(1887-1898) ; Erlangen, 250 ; and in the canton of Lucerne, 204 (1898). 

With these phenomenally high rates, it is interesting to compare the 
following exceptionally low ones viz., Croatia and Sclavonia (provinces 
of), 16 ; Valais (canton of), 16 (1898) ; Shetland Isles, 16 (1874) ; Cagliari, 
18 (1887-1891) ; Dalmatia (province of), 19 ; Sardinia, 19 ; Ajaccio, 19 ; 
Corti, 20 ; Oviedo (province), 21 ; Kerry (county), 27 etc. 

It has long been a moot question whether malignant tumours are of 
more frequent occurrence in urban or in rural districts ; and even in 
modern times, with the aid of statistical data, the answers given to this 
question are not always unanimous. 

Unfortunately, the English national statistics, so excellent in most 
respects, contain no data bearing directly on this important subject ; 
but, from such crude information as can be indirectly gleaned, it appears 
that at the present time the disease is as frequent in the rural districts 
as in the towns. 

As long ago as 1838, William Farr investigated this subject, and found 
that the cancer deaths in the rural districts were, to those in the towns, 
in the ratio of 1 to 0-97. Walshe soon afterwards, basing his calculation 
on information contained in the Registrar-General's reports for the years 
1838-1841 (which comprised the metropolis and twenty-five towns on the 
one hand, and a number of rural districts on the other), found that the 
cancer mortality in the rural districts then was 19-8 per 100,000 living, 
and in the towns 18-3. 

1 Exclusive of sarcoma. 2 And district. 3 Population 379. 



28 THE NATURAL HISTORY OF CANCER 

When these estimates were made, 65 per cent, of the population lived 
in the country. Now, however, such has been the rapid increase of 
urbanization, only 23 per cent, of the population dwell in the country, 
and of these a large proportion really belong to the towns in whose 
suburbs or vicinity they reside. Indeed, so thoroughly urbanized is the 
country at the present time, that differential vital statistics as between 
town and country have lost much of their significance. 

Tatham has investigated this subject, on the basis of the statis- 
tical data for the year 1901. He found that, at ages above thirty-five, 
the crude and corrected (for sex) cancer mortality per 100,000 living, in 
urban and rural districts, was as follows : 

Crude Rate. Corrected Rate. 

Urban 246 .. ..260 

Rural 268 .. ..234 

In Scotland, where for many years the national statistics have been 
kept in such a way as to facilitate comparisons of this kind, cancer is 
more prevalent in the towns than in, the country ; but the distinctions 
are not very marked, probably because the Scotch people, like the 
English, have been so completely urbanized over 75 per cent, of them 
being massed in the towns that few parts of the country are exempt 
from urbanizing influences. Cancer is least prevalent in the islands, 
where the conditions are purely rural, the people are poor, and the alimen- 
tation is mainly vegetarian. 

The following figures showing the cancer death-rates illustrate this : 

1905. 1900. 1891. 18SS. 

Principal towns .... 92 .. 84 70 63 



Large towns . . . . 80 . 70 

Small towns . . . . 79 . 77 

Midland rural districts . . 99 . 83 

Insular rural districts . . 79 . 56 

Average for all Scotland . . 89 . 81 



Ireland is the least urbanized and poorest part of the United Kingdom, 
and it accords with the foregoing indications that it is also the least 
prone to cancer ; and when the corresponding cancer death-rates have 
been corrected for diversities in age and sex distribution, this comparative 
immunity is seen to be even more marked than it at first appeared to be. 

The highest Irish cancer mortality is met with in well-to-do Ulster, 
which comprises the large city of Belfast, where the population is largely 
of Scotch descent and of Scotch habits ; but the rural division of Armagh 
has the highest cancer death-rate viz., 104 (1897-1901). Next in order 
come the counties of Dublin (84) and Londonderry (82), each comprising 
a large town ; while the lowest rates are in the wild and poverty-stricken 
West-in Kerry (26), Mayo (36), and Clare (38), the figures being for the 
period 1897-1901. 

The French statistics 1 illustrate similar conditions in a very striking 
way, although they give no information for the rural districts, except as 

-R Vif r rTT 1 , 1 fficial P ublications relating to this matter, I am indebted to M. le Dr. J. 
^ertillon, Lhef des travaux statistiques de la ville de Paris ; and to M. Monod, Directeur de 
1 Assistance et de 1'hygiene publiques, to both of whom I tender my thanks 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 



29 



to the small towns known as chefs-lieux d'arrondissement. 
years 1895 and 1900, the figures were as follows : 

1895. 

Paris 119 

All towns of above 100,000 inhabitants . . . . 108 

All towns of from 100,000 to 30,000 . ... 96 

All towns of from 30,000 to 20,000 inhabitants . . . 92 

All towns of from 20,000 to 10,000 . ... 94 

All towns of from 10,000 to 5,000 . ... 73 

Chefs-lieux d'arrondissenient of under 5,000 inhabitants 68 



Thus, for the 



lf-00. 

121 

112 

99 

95 

91 

74 



For Prussia, Laspeyres 1 has given the following table, which is based 
on the official returns for the period 1891-1895 : 



Large towns 
Medium-sized towns . . 
Small towns 
Towns in general 
Rural districts in general 
Prussia (average for whole) 



In Austria, the cancer mortality for the towns presents a similar 
gradation (Kolb). 

For the towns of Bavaria, the cancer death-rate is 120, and for the 
country 80. 

For Saxony, the corresponding figures are, for the towns 106, and for 
the country 89 (Prinzing). 

In Norway, the cancer death-rate for the towns, in 1897, was 100 ; and 
for the rural districts 80 (Geirsvold). 

Of twenty-three Dutch towns of over 20,000 inhabitants (1897-1900), 
fourteen had a cancer death-rate above the average for the whole country 
(De Bo vis). 

These data prove that the inhabitants of towns, and especially of the 
large towns, are more prone to cancer than those of the small towns and"* 
of the rural districts. There are, however, exceptions, as may be gathered 
from study of the previously cited data. Moreover, in Switzerland, 
Denmark, Sweden, Norway, Bavaria, and Baden, all of which have very 
high cancer death-rates, the conditions of existence are predominantly 
rural ; whereas England, Scotland, and Belgium, whose populations are 
more completely urbanized than those of any other communities, mani- 
fest only moderate proclivity to the disease. Among the towns similar 
occurrences are noticeable e.g., Geneva, Rouen, Lyons etc., have higher 
cancer death-rates than Berlin, Paris, or London ; the cancer death-rates 
of Danzig and Keil surpass those of Berlin ; while Florence and Ravenna 
have a^greater proclivity to cancer than Rome etc. 

If it were possible to correct these various death-rates for diversities 
of age and sex distribution, for the presence of hospitals and other dis- 
turbing factors, some of these anomalies might then be less conspicuous ; 
but, even so, the main indications of the crude data would not be changed. 
Thus, as Laspeyres has shown, the cancer death-rates of men from sixty 
to seventy years old, in the large towns of Prussia, amounted to 68 ; 
whereas the corresponding figure for the rural districts was only 23-7, 
and at all other age periods similar differences were noticeable. These 
1 Central.- Bl. f. ailg. Qesundheitspftege, 1901, S. 342. 



30 THE NATURAL HISTORY OF CANCER 

differences cannot be explained as the result of presumed better diagnosis 
by the urban medical practitioners, as I shall subsequently have occasion 
to prove. Therefore, it seems clear that, in modern communities, urban 
populations are generally more prone to malignant disease than are the 
rural inhabitants. In Sweden, however, as in England, it has been noted 
that the cancer death-rate of the small towns surpasses that of the large 
ones ; which, with other similar indications, seems to show that the 
incidence of the disease is determined more by the local conditions of 
existence, than by urbanization or ruralization per se. 

Here, however, it is necessary to point out a peculiar feature of 
cancer, wherein it differs from nearly all contagious diseases viz., that 
its incidence never shows any proportional variability with mere density 
of population. This was long ago shown to be the case for our country 
by Walshe, C. H. Moore, and Haviland. In this respect cancer differs 
markedly from tubercle. 

By comparing the figures showing the density of population in 
European communities, with those indicating the corresponding cancer 
death-rates, very striking disparities in this respect are at once revealed. 
Thus, Belgium and England, with 550 and 540 inhabitants respectively 
to a square mile, are the most densely populated communities in Europe ; 
but they are far from occupying a similarly exalted position in the cancer 
list; and, although nearly equal as regards density of population, their 
proclivity to cancer shows no corresponding similarity. Switzerland and 
Denmark, which head the cancer list, have only a medium density of 
population viz., 197 and 146 per square mile respectively. On the 
other hand, Norway and S\veden, the most sparsely populated countries 
in Europe, with less than thirty inhabitants per square mile, have very 
high cancer death-rates. 

This peculiarity in the incidence of cancer tells against contagion, as 
the causative factor of variations in its distribution ; and points rather to 
diversities in the conditions of existence, and especially to such as are 
independent of mere density of population. 

General Survey of the Distribution of Cancer in Asia. 

All available indications point to the conclusion, that cancer is every- 
where much less prevalent in Asia than in Europe. 

Nearly all the old writers on the geographical distribution of disease 
agree in stating, that cancer is more prevalent in China than in any other 
Asiatic community. With regard to recent sources of information, the 
mean annual death-rate from cancer in Hong-Kong for the period 1895- 
1904, was 4-45 per 100,000 inhabitants ; 1 while that for England and 
Wales, during about the same period, was 81. 

Of 2,981 Chinese adults admitted in the Tang Wah Hospital at Hong- 
Kong in 1900,2 8 had malignant tumours ; and of 3,185 admitted in 
1902, 3 10 were similarly affected: thus, of these 6,166 inmates, 18 had 
cancer, or 1 in 342. 

1 Report on Cancer in British Colonies, 1906. 
Report of the Civil Medical Officer, 1900 

fiJ&iS 19 \ The Tan S Wah Hos P ital w a kind of refuge 
f the Chinese go when very ill or moribund. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 31 

Of 1,299 Asiatics admitted into the Government Civil Hospital at 
Hong-Kong in 1902, 11 had cancer, or 1 in 118. 

In London general hospitals the proportion of inmates affected with 
cancer has lately been estimated at 1 in 20. 

Of the 1,305 deaths of Chinese in Hong-Kong hospitals during the 
year 1902, only 3 were due to cancer, or 1 in 435. 

A few years ago I wrote to Dr. Cantlie, who was then Government 
surgeon at Hong-Kong, asking him for information on this subject. He 
very obligingly replied as follows : " I do not think I have been without 
a case of malignant disease under my care ever since I came to China 
six years ago." Of 3,608 consecutive Chinese hospital in-patients under 
his care, 114 had malignant disease, or 1 in 31. Of Cantlie's 114 Chinese 
cancer patients, the primary seats of the disease were as follows : female 
breast, 38 ; upper jaw, 25 ; lower jaw, 14 ; penis, 9 ; uterus, 8 ; parotid, 5 ; 
hip, 5 ; tongue, 4 ; lip, 3 ; and thigh, 3. At Dr. Kerr's hospital in Canton, 
during the year 1887, 30 cases of malignant tumours were operated on, 
including 11 amputations of the female breast. Strange to relate, Cantlie 
has never met with cancer of the stomach among the Chinese. With 
regard to their diet, he says : " All Chinamen eat fish and pork at morning 
and evening meals. Fowls and ducks are always on the table of all but 
the most humble of the coolie class, and they do not have them because 
they cannot afford them. I hope this will be a sufficient answer to those 
who maintain that Chinamen live on rice. It is not nearly so true as 
that the Scotch live on porridge." 

In the Hong-Kong district, non-malignant tumours seem to be even 
rarer among the Chinese than the malignant ones, for of 6,166 hospital 
inmates, only 8 were thus affected. On the other hand, malarial maladies 
are very common, and tubercle is prevalent, according to Dr. W. Hunter. 

Dr. J. P. Maxwell x has lately published some valuable information 
as to the prevalence of malignant tumours in the province of Fokien, 
South China, which is situated just outside the tropical zone. 

During three and a half years, 11,000 patients were seen at the Chang- 
poo Hospital ; and of these, 54 (males 42, females 12) were subject to 
these maladies, or 1 in 203. Of the males, 24 suffered from cancer 
(oesophagus, 7 ; pylorus, 2 ; rodent ulcer of the face, 3 ; penis, 2 ; and 
1 each as follows : lip, palate, leg, jaw, tongue, face, scalp, eyelid, thyroid, 
and groin) ; and 18 from sarcoma (femur periosteal, 3 ; spindle-celled of 
connective tissue, 4 ; neck, 5 ; and 1 each in the following situations : 
antrum, upper jaw, lower jaw, naso-pharynx, testis, and skin of back 
melanotic). Of the females, 7 had cancer (breast, 4 ; oesophagus, 1 ; and 
rodent ulcer of the face, 2) ; and 5 had sarcoma (axilla, 1 ; lymphadenoid, 
1 ; upper jaw, 1 ; neck, 1 ; and lung, 1). 

The population furnishing these cases lived chiefly on rice, only a 
small amount of animal food and alcohol being consumed. 

According to Dr. Elizabeth Reifsnyder, 2 of Shanghai, cancer of the 
uterus and breast is common in that part of China, and ovarian cystomata 
are also often met with. 

1 Journal of Tropical Medicine, September, 1904, p. 270. 

2 American Journal of Obstetrics, etc., vol. xxxi., 1895, p. 512. 



32 THE NATURAL HISTORY OF CANCER 

In his interesting " Notes on Surgical Practice among the Natives of 
Shanghai," Dr. E. Henderson 1 points out that the establishment of mission 
hospitals, giving gratuitous treatment, has proved that cancerous and 
sarcomatous tumours are not uncommon among the natives of that 
vicinity. Non-malignant tumours (lipoma, etc.) of exceptionally large 
size are also fairly often seen, owing to the inabilityof native practitioners 
to remove them. He reports cases of fibre-cystic sarcoma of the lower 
jaw and of the parotid region, under his own observation. Tuberculous, 
malarial, and syphilitic affections are very rife The staple diet com- 
prises rice and other vegetable products, with fish, pork, or fowl if means 
permit. Tea is the usual drink, and samshu, a native spirit made from 
rice, is also freely taken, but hardly ever to such an extent as to cause 
drunkenness. 

According to a recent publication by Dr. Brunet, 2 cancer is com- 
paratively uncommon in those parts of China where the bulk of the 
people live on an almost exclusively vegetarian diet, being too poor to 
purchase any of the various flesh foods which are there used for culinary 
purposes. He points out that the Chinese altogether eschew milk as 
food, even for infants ; and it is a mistake to suppose that the majority 
of them live on rice, as this staple can only be afforded by families whose 
means are above the average, most of the population having to be 
satisfied with cheaper grains, such as millet. 

Dr. Gray 3 reports that cases of cancer of the mamma, lip, and penis 
are often seen at the mission hospitals in North China. 

At the hospital for Chinese in Tartar City, Pekin, Dr. Foulkes 4 
found that cancer was fairly common. He mentions cases of epithelioma 
of the lower lip and oesophagus, and spindle-celled sarcoma of the breast 
in a girl aged seventeen. 

In the United States (1900), 5 the 48,565 Chinese (mostly adult males) 
comprised in the registration area, had a cancer death-rate of 49 per 
100,000 living, or about 1 in 40 of the total mortality from all causes. 
They experienced very heavy mortality from phthisis and pneumonia, 
but the deaths from malaria were very few. For the white population, 
the cancer death-rate for all ages and both sexes was 66 (males 50). It 
would seem, therefore, as if the change of habitat had greatly increased 
the liability of the Chinese immigrants to malignant disease. A similar 
occurrence has been noted in Australia, with respect to the Chinese coolie 
immigrants in Victoria. 6 

Malignant tumours are believed to be less prevalent in Japan than 
in China ; however, according to a recent estimate, the Japanese cancer 
death-rate is placed at 49 per 100,000 living, but on what evidence this 
figure rests I am unable to say. 

It accords with the above-mentioned belief, that the Japanese immi- 

1 Edinburgh MedicalJournal, vol. xxii., 1876, pp. 405, 690 ; and vol. xxiii., 1877, p. 118. 

2 fievue d' Hygiene, t. xxvii., Nos. 2 and 3, 1905. 

3 Lancet, 1901. 

4 Indian Medical Gazette, September, 1902, p. 348. 

6 Twelfth Census Report of the United States (1900). 

6 Lancet, vol. i., 1904, p. 424; also Australian Medical Gazette, September 21, 1902. 
p. 169. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 33 

grants in the United States are less prone to these diseases than the 
Chinese, their cancer death-rate in 1900, being 24 per 100,000. The 
Japanese subsist mainly on rice, beans, millet, and other vegetable pro- 
ductions, to which those who can afford it add fish, eggs, small quantities 
of meat etc. They are of very frugal and temperate habits, andr arely 
indulge in alcoholic drinks. 

In Korea, malignant tumours are not common, but most of the chief 
local varieties have been met with. 

Nothing definite is known as to the incidence of these maladies in 
Northern Asia and Siberia. 

In Arabia, Persia, and Asia Minor, cancer is reported to be rare 
(Lombard) ; but in the Caucasus it is by no means uncommon, especially 
among Russians and Armenians. In the adjacent province of Astrakhan 
cancer is moderately prevalent, and tubercle is common (Dallinger). In 
Cyprus* 49 cases of malignant and 100 of non-malignant tumours, were 
met with among about 30,000 hospital and dispensary patients, during 
1903. 

In the absence of statistical reports as to the incidence of malignant 
tumours and other diseases among the immense population of India, 
which in its entirety approximates 350,000,000, all estimates must be 
regarded as tentative and conjectural. The great extent of the country 
and its teeming millions make it very difficult, even for those who have 
been long resident there in a professional capacity, to arrive at correct 
conclusions. The few hospitals and dispensaries in India draw their 
patients from immense multitudes and vast areas, so that, although 
many cases of cancer may be constantly under treatment, the propor- 
tionate prevalence of the disease in the general population may be much 
less than the medical officers of such institutions are apt to believe. After 
careful study of all available sources of information, it appears to me 
clearly indicated that malignant tumours are very much less prevalent, 
pro rata, in India than in Europe ; but neither the Hindoos, who number 
over 200,000,000, nor the Mohammedans, who number over 60,000,000, 
nor any of the other races of India, can claim exemption. 

A recently issued Government Report, based on the percentage of 
cancer cases to the total number of all diseases treated in the hospitals 
and dispensaries of the various provinces, gives the following results ; 
but, for the reasons above stated, the incidence of the disease in the 
general population is certain to be very much less than in these hospital 
and dispensary patients, low as this ratio is : 

Proportion of Cancer 

Provinces. Cases to 100 of all 

other Diseases. 

Punjab O'TOO 

Central division . . . . . . . . . . . . 0'700 

Berar O'TOO 

Burmah 0'610 

Agra and Oudh O'OoO 

Bombay - 050 

Bengal 0'025 

Madras 0'024 

Assam O'OOS 

1 Colonial Report, 1903. 



34 THE NATURAL HISTORY OF CANCER 

In interpreting these figures, it is necessary to remember that the 
patients were nearly all adults, the men being three or four times as 
numerous as the women, who are with difficulty persuaded to avail 
themselves of hospital treatment. 

In a general way, it may be said that all the varieties of malignant 
tumours met with in Europe have their counterparts in India. My 
statistics show that in English hospital patients 85-4 per cent, of these 
growths are epithelial cancer, the remaining 14-6 per cent, being sarcomata. 
Most Indian statistics, however, reveal a much greater relative proportion 
of the latter ; indeed, the data from some districts seem to show that sarco- 
mata are nearly as prevalent as carcinomata. A remarkable negative 
feature of the Indian Reports, is the almost complete absence from them of 
cases of malignant disease of the stomach (pylorus) ; and an equally note- 
worthy positive feature, is the unusually great predominance of external 
cancers. 1 Mammary, uterine, and hepatic cancers, seem to be relatively 
much less prevalent in India than in England. The extraordinary com- 
parative frequency of some external reputed manifestations of the disease 
in India, such as " cancer " of the penis and cutaneous system, especially 
the curious " Kangri-burn cancer," is so unparalleled in European experi- 
ence, and these lesions seem in other respects so different from epithelial 
cancer, as it is met with in this country ; that I suspect the majority of 
them will eventually turn out to be pseudo-malignant lesions due to 
microbic infection rather than true cancer, as I shall subsequently have 
occasion to point out more in detail. 

The data available do not enable us to determine the comparative sex 
prevalence of the disease, owing to the great majority of hospital patients 
being males, the inhabitants of India being very averse to their women 
entering hospitals. 

Some valuable information as to the incidence of malignant disease 
in the Punjab and at the Mayo Hospital, in Lahore of that province, has 
lately been published by Dr. D. W. Sutherland. 2 He concludes that 
cancerous affections are not at all common in this part of India. In all 
the Punjab hospitals and dispensaries for the years 1899-1903, the 
yearly average of patients treated for malignant tumours was 266, and 
the proportion of these tumours to the total cases treated for all diseases 
was only 0-08 per mille. 

At the Mayo Hospital in Lahore, during the decennium 1892-1903, 
43,412 in-patients were treated ; and of these, 792 had some form of 
malignant tumour (carcinoma, 400 ; sarcoma, 334), or 1 in 55. These 
patients were drawn from the 25,000,000 of the Punjab, every part having 
contributed, and some even came from adjoining States. 

In the population of the Lahore district, Hindoos and Mohammedans 
are about equally represented, and both races proved to be about equally 
liable to malignant disease ; but with respect to carcinoma, the Hindoos 
were eighty cases in excess of the Mohammedans, owing to individuals of 

/ -f^ TJ! ?t nCer fr m , India anal y sed b y the Imperial Cancer Research Fund 

kipLn^f e su e f the body> and niy 7e internai rgans 

2 Arch. Middlesex Hosp., vol. iii., 1904, p. 84. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 35 

their race furnishing seventy-two cases of " cancer " of the penis, whereas 
there was not a single case of this local variety of the disease among the 
Mohammedans. The latter practise circumcision, and Sutherland ascribes 
their immunity from this local form of the disease to this custom. The 
proportion of cases of carcinoma of the penis in the Hindoos, is so enor- 
mously in excess of what is met with in Europe, that I wonder if the diag- 
nosis may not be in fault. Is it quite certain that in most of these cases, 
we may not have to do with a form of contagious venereal condyloma,y x 
to which the well-known libidinous practices of the Hindoos render them' . 
specially liable ? * 

Syphilis and malaria are of great frequency among the populations 
whence these patients came, but insanity and tubercle are rare. With 
regard to their diet, both races are mainly vegetarian, taking only a 
little flesh food on the occasions when they can afford it. Alcoholic 
drinks are tabooed by the Mohammedans, but the Hindoos indulge freely 
in them. Nearly half of the total patients were employed in cultivating 
the soil, much smaller numbers were shop-keepers, general labourers, 
beggars, etc. The maximum age of prevalence for carcinoma was from 
forty to fifty (114 cases out of 395) considerably earlier than in Eruope ;)^ 
and for sarcoma, of 350 patients, 79 were from thirty to forty years old, 
68 from twenty to thirty, 58 from forty to fifty, and 44 from ten to twenty 
years old. 

With regard to the localization of the disease, the most striking fact, 
next to the frequency of " cancer " of the penis in the Hindoos, is the "X v 
complete absence of malignant disease of the stomach, of which not a 
single instance is recorded. 

The chief seats of carcinoma in 396 cases (males 270, females 126) 
were : penis, 72 (all Hindoos) ; skin, 58 ; breast, 50 ; rectum, 30 ; uterus, 
23 ; liver, 23 ; tongue, 20 ; lip, cheek, mouth, and palate, 13 ; bladder, 6 ; 
pharynx, 5 ; larynx, 5 ; anus, 5 ; intestines, 3 ; rodent ulcer, 3 ; pancreas, 
3 ; oesophagus, 2 etc. 

The chief seats of sarcoma in 334 cases (males 255, females 79) were : 
head and neck, 112 (jaws, 53 ; face, 13 ; orbit, 13 ; nose, 10 ; naso- 
pharynx, 9 etc.) ; lower limbs, 59 (thigh, 17 ; leg, 13 ; knee, 9 ; foot, 7 
etc.) ; upper limbs, 24 (shoulder, 7 ; arm, 6 ; elbow, 4 ; forearm, 4 ; hand, 
3 etc.) ; trunk, 21 (abdomen, 7 ; back, 7 etc.) ; various organs (testis, 8 ; 
parotid, 5 ; ovary, 3 ; tongue, 2 ; breast, 1 etc.). 

In the above, twenty-eight cases of sarcoma of the long bones are 
comprised. 

All the different histological varieties of carcinoma and sarcoma were 
represented. 

In Kashmir, a state adjacent to the Punjab, with a population of 
several millions, malignant and other tumours are, according to Dr. E. F. 
Neve, 2 not particularly rare for India. 

This country is a high-lying valley, surrounded by high mountains, 
of which extensive tracts are permanently under water, while large areas 

1 Referring to cases of this kind in Egypt, where cancer is phenomenally rare, 
Dr. Madden says : " Condylomata flourish with truly tropical luxuriance." 

2 Indian Medical Gazette, May, 1902, p. 164. 

32 



36 THE NATURAL HISTORY OF CANCER 

are liable to annual floods. During the summer season the valley is 
practically an alluvial plain covered with rice-fields and swamps, yet 
malaria is rare. Phthisis, pleurisy, and pneumonia are also rare, but 
rheumatic affections are prevalent. The people, who are Hindoos, live 
mainly on rice, the cultivation of which is their staple employment. 

During the decennium 1890-1899, 2,020 natives with tumours were 
operated on at the Kashmir mission hospitals, more than half of which 
were malignant. 

Of 486 epithelial cancers, the sites were as follows: "Kangri-burn 
cancer " (skin of abdomen, thigh, or vicinity), 363 ; female breast, 29 ; 
leg, 21 ; chest, 13 ; eyelids, 6 ; lip, 5 ; head, 5 ; face, 4 ; foot, 3 ; heel, 3 ; 
wrist, 3 ; rectum, 3 ; eyeball, 3 ; ear, 3 ; nose, 2 ; neck, 2 ; back, 2 ; penis, 
2 etc. Those attacked were the mature and elderly. 

As compared with Sutherland's statistics for the adjacent Punjab, 
some extraordinary diversities in localization are noticeable. In the 
first place, Neve tells us that more than three-fourths of all his epithelial 
cancers were of the peculiar " Kangri-burn " variety. During the cold 
winter, for the sake of warmth, the natives carry under their clothes, in 
contact with the lower part of the abdomen, a charcoal fire-basket 
(" Kangri "). This often causes burns of the skin of the abdomen, thigh, 
etc. As the result of constant irritation by the " Kangri," the resultant 
scars often become converted into thickened, raised excrescences, which 
eventually ulcerate. Foul, excavated, spreading ulcers, with thick raised 
edges, thus result. The adjacent lymph-glands become similarly affected, 
and often even the axillary glands as well. Death is commonly caused 
by septic complications, secondary to these sloughing ulcers, which some- 
times perforate large bloodvessels, and prove fatal in this way. Excision 
of the disease in its early stage is absolutely curative ; but after the glands 
have become extensively involved, only 50 per cent, of those operated 
on can be completely cured. The important question arises : What is 
the real nature of this malady, which is so different from ordinary 
epithelial cancer in its main features ? According to Neve, it is cutaneous 
epithelial cancer, the hard fibrous base of the ulcers being infiltrated and 
overlaid by masses of epithelial new-formation, containing abundant 
" nests," etc. In all this, it seems to me, we scarcely have sufficient 
evidence of cancer, especially in view of the clinical course of the malady, 
its curability by operation, and the absence of metastases. The disease 
is probably more akin to keloid than to cancer ; and, like the former, 
it is probably due to microbic infection. 

If this peculiar affection is removed from the list of cancer, it will be 
seen that the latter malady is exceptionally rare in Kashmir. 

Another noteworthy feature of Neve's statistics, compared with those 
of the Punjab, is the relative rarity of cancer of the penis. The uncir- 
cumcised of Kashmir have no special proclivity to this local variety of 
the disease, which supports my above-mentioned contention as to the 
non-cancerous nature of most of the Punjab penile cases. 

The Kashmir data agree with those from the Punjab, in indicating 
great rarity of visceral cancer, specially of the stomach, liver etc. 

With regard to sarcoma, of 154 cases, 23 were unclassified as to 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 37 

locality ; of the others the sites were : gum (epulis), 21 ; neck, 12 ; 
parotid. 12 ; lower jaw, 9 ; upper jaw, 7 ; orbit, 1 6 ; leg, 6 ; groin, 5 ; 
thigh, 5 ; forearm, 5 ; palate, 3 ; base of skull, 3 ; chest, 3 ; back, 3 ; 
elbow, 3 ; foot, 3 etc. 

The most noteworthy feature of this list is the frequency of malignant 
" epulis." A few of the patients were young children. 

Of 692 non-malignant tumours, the distribution was as follows : 
papilloma, 120 ; unclassified, 120 ; polypi, 114 ; lipoma, 106 ; fibroma, 57 ; 
granuloma, 38 ; horny, 29 ; naevus, 27 ; neuroma, 25 ; keloid, 18 ; chon- 
droma, 9 ; osteoma, 6 ; lymphoma, 5 ; goitre, 4 ; myxoma, 2 ; molluscum 
fibrosum, 1 etc. 

Of 213 cysts, the following subdivision is given : sebaceous, 124 ; 
ranula, 34 ; ovarian, 15 ; cystic goitrej 15 ; dermoid (mostly periorbital), 
12 ; hydatid, 8 ; serous, 7 ; lactic, 2 ; mesenteric, 2 ; pancreatic, 1 ; 
parotid, 1 etc. 

It is remarked of the sebaceous cysts, that they were singularly ^ 
common in certain villages. A great many hydroceles (298) and ganglions 
(44) were also noted. 

In Assam, according to Dr. Dalgetty, 2 malignant tumours are very 
rare. His experience relates to Adampore, in South Sylhet. During five 
years' work in this district, among a labouring population of 12,000 
Hindoos men, women, and children imported from various parts of 
India to work in the tea-gardens, he met with only eight instances of 
malignant disease. These comprised six of cancer viz., four males (one, 
aged thirty-five, of the tongue ; one, aged forty-five, of lip ; one, aged 
thirty-five, of mouth ; one, aged thirty, of penis) and two females (both 
of the cervix uteri, at about the age of forty) ; and two of sarcoma (one, 
aged thirty-five, of the palmar fascia ; one, aged thirty-five, of the rib). 

Among these Hindoos, 2 cases of ovarian cystoma, 1 of uterine myoma, 
and 1 of lipoma of the breast, were also met with. 

Of 15,000 resident natives, mostly Mohammedans, only three cases 
of malignant tumours were seen during the same period viz., a male, 
aged fifty, with cancer of the lip ; a male, aged thirty-five, with sarcoma 
of the scalp ; a male, aged thirty, with melanotic sarcoma of the eye. 
One case of cystic myoma uteri was also seen. 

Both sexes anoint the whole body with cocoanut oil ; and are very 
free from warts and other cutaneous blemishes. 

The district is highly malarious, and it may be safely asserted that 
every one of the above patients with malignant tumour had suffered from 
malaria. 

Dr. Drake, 3 during several years' practice in the Thakurbarrie district 
of Assam, when he was in charge of several thousand coolies from various 
parts of India, as well as of the natives of the vicinity, testifies as to the 
rarity of malignant tumours ; for he never saw a single case. 

A valuable statistical study of the incidence of cancer among natives, 

1 In a recent publication Dr. Xeve mentions the eye as also a fairly common seat of 
sarcoma in Kashmir. British Medical Journal, vol. i., 1906, p. 1217. 

2 Journal of Tropical Medicine, April 15, 1902, p. 122. 

3 Lancet, vol. ii., 1904, p. 1309. 



38 THE NATURAL HISTORY OF CANCER 

in the surgical wards of the Medical College Hospital of Calcutta, during 
the nine years 1896-1904, has been published by Dr. Megaw. 1 In this 
series, the cases of cancer occurring in the medical and gynaecological 
wards of the hospital are not comprised. 11,446 surgical hospital patients 
furnished 343 cases of malignant tumours (1 in 33, or 3 per cent, of the 
total admissions). The natives of India are very loath to come to 
hospitals unless afflicted with very serious disease hence "it is only 
natural that malignant tumours should bulk larger in Indian statistics 
than in those for Europe." The local conditions in the two cases are, 
in fact, so different that " no fair comparison as to the relative prevalence 
of the disease in India and Europe can be based on the above data." 
Although the carcinomatous form of the disease was more frequently 
met with than the sarcomatous, yet the ratio of the latter to the former 
was much higher than in Europe. The site-incidence percentage for 
carcinoma was as follows : penis and scrotum, 20 ; female breast, 19-9 ; 
integument, 15-2 ; ant rum and palate, 9-9 ; rectum, 1-7 ; rodent ulcer, 1-7 ; 
tonsil, pharynx, and larynx, 1-7 ; stomach, 0-9 etc. For sarcoma the 
usual seats were : leg, 18-7 ; neck, 18-7 ; arm and axilla, 12-8 ; jaws and 
antrum, 10-1 ; wall of trunk, 7-2 ; testes, 5-4 ; face, 5-3 ; breast, 3-9 ; 
pharynx, 3-4 ; abdominal cavity, 3-4 ; pelvis, 2-9 etc. 

The Hindoos were found to be more frequently affected with malignant 
disease than the Mohammedans, mainly owing to their greater proclivity 
to a few special local forms of the disease viz., to " cancer " of the penis, 
sixty-four Hindoos being thus affected, and only two Mohammedans ; to 
mammary cancer, fifty-seven Hindoo females being affected, as compared 
with only four Mohammedans, the latter having great reluctance to 
hospital treatment for their women. Hindoos were also more prone to 
cancer of the mouth, cheek, and jaws than the Mohammedans, in the 
proportion of 49 to 1, although both alike indulged in betel-chewing, to 
which this form of disease has often been ascribed. 

Dr. McLeod, 2 from experience in Calcutta hospitals, concludes that 
malignant tumours are comparatively common among the natives of 
Bengal, both in hospital and private practice : in females the breast being 
chiefly affected, and in males the cutaneous system, oral cavity, and 
especially the penis. Of 254 tumours operated on at the Medical College 
Hospital in Calcutta (1879-1883), 49 were malignant ; and of 333 tumours 
(1886-1890), 87 were malignant. Considering that the Bengal popula- 
tion, whence these hospital cases were derived, numbers over seventy 
millions, the proportion of cancer cases in these hospital statistics is sur- 
prisingly small. 

According to Davidson, 3 cancer is very rare in Bombay, only 0-1 per 
1,000 of the total deaths being due to this cause. 

Dr. Niblock * has tabulated all the malignant tumours treated at the 
Madras General Hospital, during the ten years 1892-1901. To this 

* Indian Medical Gazette, May, 1905, p. 103. 

"Operative Surgery in Calcutta," 1885, p. 102; also "International Text-Book 
of Surgery," vol. ii., 1900, p. 1206. 

' "Geographical Pathology," 1892. 
4 Indian Medical Gazette, April, 1902, p. 161. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 39 

hospital patients come not only from the city of Madras, which has 
500,000 inhabitants ; but also from all parts of the Madras Presidency, 
which comprises a population of over 40,000,000, of whom three-quarters 
are Hindoos, and the rest chiefly Mohammedans. During the decade 
under consideration, 4,270 patients were treated for malignant tumours, 
or about 2-5 per cent, of the total admissions. From these figures it may 
be concluded that malignant disease is very rare in Madras. 

Of 976 carcinomata (males 746, females 230), the localization was as 
follows : mouth, 411 (males 314, females 97) ; penis, 200 (all Hindoos) ; 
tongue, 64 (males 58, females 6) ; breast, 44 (all Hindoos except one 
Mohammedan female ; males 5, females 38) ; uterus, 46 (all Hindoos) ; 
jaws, 34 (males 30, females 4) ; rectum, 33 (males 27, females 6) ; 
stomach, 21 (all Hindoos ; males 14, females 7) ; liver, 18 (males 15, 
females 3) ; skin of lower limbs, 17 (males 11, females 6) ; rodent ulcer, 4 
(males 3, females 1) ; and vagina, 3. 

A noteworthy feature about the above data, is the very large propor- 
tion of cases of carcinoma of the mouth and tongue which they comprise, 
amounting to nearly half of the total. Niblock attributes this to the 
prevailing habit of " betel "-chewing. Among the inmates of the Lahore, 
Kashmir, and Assam hospitals, this local form of cancer was very little in 
evidence, and one wonders whether " betel "-chewing prevailed among 
them. Here, again, we meet with a very large proportion of cases of 
" cancer " of the penis, all among Hindoos, as at Lahore. The Hindoos 
of the great cities of India seem to have special proclivity for this local 
variety of the disease, but nothing of the kind is noticeable in the more 
rural districts of Assam and Kashmir. 

Of 4,903 Hindoo patients, 97 had carcinoma, or 1-98 per cent. ; while 
of 339 Mohammedan patients, 6 had carcinoma, or 1-76 per cent. 

The Eurasians seemed to be less subject to cancer than any other 
native race ; and, among the Hindoos, several of the patients were 
Brahmins. 

Of 293 sarcomata (males 217, females 58, children 12), the sites of 
the disease were as follows : lower limbs, 70 cases (males 58, females 11, 
children 2) ; neck, 35 (males 24, females 9, children 2) ; jaws, 33 (males 24, 
females 9) ; upper limbs, 27 (males 25, females 2) ; trunk, 17 (males 12, 
females 3, children 2) ; face, 15 (males 9, females 3, children 3) ; scalp 
and skull, 13 (males 9, females 4). 

Of the Hindoo hospital inmates, 0-67 per cent, had sarcoma ; and of 
the Mohammedans, 0-49 per cent. 

Among the natives of Ceylon, malignant tumours are very rare, the 
death-rate from this cause in 1897, being 5 per 100,000 inhabitants, or 
1 in 563 of the total deaths. Of 63,030 patients treated at the chief 
hospitals ! in 1900, 248 had some form of malignant tumour, or 1 in 254 ; 
and of 6,501 deaths of the hospital patients, 27 were due to malignant 
tumours, or 1 in 241. In the same year, 256 cases of non-malignant 
tumours were under hospital treatment. 

According to Sir A. Perry,2 the cancer mortality in 1903, was 1 in 
every 16,820 persons living, or about 6 per 100,000 inhabitants, the com- 

1 Colonial Report, Xo. 19, 1902. 2 Report on Cancer in British Colonies, 1905. 



40 THE NATURAL HISTORY OF CANCER 

monest seats being the oral cavity and penis. The island is highly 
malarious. Tubercle is rare, the death-rate from this cause in 1903, 
being 91 per 100,000 living. 

In Burmah and Siam, malignant tumours are perhaps rather more 
prevalent than in India. During four years' residence in Siam, Gowen 1 
met with a few cases of carcinoma and sarcoma ; but Rasch never saw a 
single case of sarcoma there. In Bangkok, according to Nightingale, 2 
although malignant tumours are seldom seen by the doctors, they are 
probably less rare than is generally believed. 

Among the Laos people, who occupy the region to the north of Siam, 
Hansen 3 found that malignant tumours were very rare. In three years' 
practice he only met with a single case. 

In the hospitals and dispensaries of the federated Malay States, 4 
during the year 1903, thirty-three deaths from malignant tumours were 
recorded, or one in fifty-eight of all the fatal cases treated. Altogether, 
during the year, 256 cases of malignant and 297 of non-malignant 
tumours w r ere under treatment. Malarial affections are very prevalent ; 
and there is a considerable tubercle incidence, especially of phthisis. 



General Survey of the Distribution of Cancer in Australasia and Oceania. 

Among the whites of Australia and New Zealand, cancer is much more 
prevalent than in any other part of Oceania, and also than in Asia ; but 
its incidence is much less than in England, the cancer death-rate per 
100,000 inhabitants for the whole of Australia being 57, or 1 in 20 of the 
total deaths (1900). 

All the local authorities state that malignant growths are so exceed- 
ing rare as to be almost unknown, among the aborigines of both these 
countries. According to G. C. Adams, 5 the Australian aborigines are 
" practically immune " from cancer. In Victoria, of seventy deaths 
among aborigines registered during the years 1894-1900, only one was 
due to cancer. These natives are, however, very prone to tubercle, and 
especially to phthisis. The Australian aborigines are a disappearing race, 
who now form only an insignificant fraction of the total population, for 
they are estimated to number less than 20,000. During ten years' experi- 
ence among the aborigines of Queensland, Dr. Roth 6 never saw a single 
malignant tumour. For a young country, the social evolution of Australia 
has of late pursued a peculiar course. Its immense territory is occupied 
by a mere handful of people some 3,750,000 of whom the great bulk 
are clotted in a few large towns on the coast of the temperate region, 
where the style of living emulated is that of the capital cities of Europe. 
Under the influence of socialistic ideas, immigration is discouraged, 
although the declining birth-rate has already fallen to such an extent as 
to endanger the future of the race. Thus, the population is almost 

1 Janus, 1896, 1897, and 1899. 

2 British Medical Journal, vol. ii., 1902, p. 835. 

3 Pacific Medical Journal, January, 1902 

4 Colonial Repoit for 1903. 

5 Lancet, vol. i., 1904, p. 424. 

6 Report on Cancer in British Colonies, 1905. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 41 

stagnant ; and it contains an unduly large proportion of adult and elderly 
persons. Under this concatenation of artificial circumstances, and with 
the aid of the lavish expenditure of borrowed millions, a high standard 
of individual material comfort has been attained in this " worker's para- 
dise." Owing to the cheapness of meat and the gluttonous habits of 
the people, the amount consumed per head is exceedingly high. Under 
these circumstances, the tubercle mortality has diminished, while the 
incidence of cancer has greatly increased. 

A curious feature with regard to cancer is that males are now more 
prone to the disease than females, the respective death-rates for 1900, 
being 59 and 55 ; and this greater proclivity of males is found in all the 
different states of the Union. 

In Australia, as in Europe, the cancer mortality of the capital-city 
districts is much higher than that of the rural districts, the rate for the 
former being 81-3 (or 6-4 per cent, of the total deaths from all causes), 
as against 44-7 for the latter (or 3-9 per cent, of the total mortality). 

Another noteworthy fact about the Australian statistics is that, like 
those of the United States, they show malignant tumours to be much more 
prevalent among immigrants than among those born in the country. 1 X 

Thus, for all Australia, the cancer death-rate in 1900, was 57-3. Of 
this total, the British and foreign-born immigrants were responsible for 
40-2, and the Australian-born for only 17-1. If only persons of thirty-five 
years of age and upwards are included, the figure for the total cancer 
death-rate will then be 195-3. Of this, the British and foreign-born 
account for 137-1, and the Australian-born for 58-2. 2 All the different 
races of immigrants in Australia, experience there a higher cancer 
mortality than prevails in their native countries. This applies, as pre- 
viously mentioned, even to the Chinese. Hence it may be concluded 
that sudden and violent changes in the environment are, per se, potent 
factors in the causation of cancer. 

The cancer death-rates for the various States in 1900, were as follows : 
Victoria, 72 ; South Australia, 59 ; New South Wales, 57 ; Tasmania, 56 ; 
Queensland, 46 ; West Australia, 30. 

In New Zealand, where the conditions of existence and of social evolu- 
tion somewhat resemble those of Australia, the leading morbid tendencies 
are also somewhat similar. Cancer and insanity have increased, and are 
increasing ; while tubercle is declining. The people are prosperous, with 
a diminishing birth-rate ; and immense quantities of flesh food chiefly 
beef and mutton are consumed. " Meat for breakfast, lunch, dinner, 
tea, supper, etc., just like the porridge-pot in Scotland," as Dr. G. Mac- 
donald, of Dunedin, wrote in answer to my letter of inquiry. In New 
Zealand, as in Australia, cancer is more prevalent among males than 
among females. The cancer death-rate for the whole country in 1900, 
was 60. 

Among the inhabitants of the South Sea Islands, cancer is most excep- 
tional. Dr. Brennan, 3 in eleven years' experience, never saw a single 
case among natives of these islands labouring in Queensland. 

1 Immigrants now total only about 15 per cent, of the entire population. 

2 Adams, op. cit. 3 Report on Cancer in British Colonies, 1905. 



42 THE NATURAL HISTORY OF CANCER 

In the Fiji Islands, 1 malignant tumours are very exceptional, since 
among the 120,000 non-European inhabitants, of whom the aborigines 
comprise nearly 98,000, the rest being Indian coolies, Melanesians, Poly- 
nesians, etc., only two deaths occurred from this cause during the year 
1900 ; and there were also only two deaths from non-malignant tumours. 
In 1903, five Fijians (two being half-castes) died of malignant disease 
viz., one of carcinoma (pylorus), and four of sarcoma (orbit, kidney, 
inferior maxilla, and face). 

Sir W. MacGregor's experience 2 is to the same effect. He says : " I 
do not remember ever having operated on a Polynesian or Melanesian 
for cancer, though I have had to do so sometimes on Europeans in Fiji." 
These people are practically vegetarians, and phthisis was not known in 
Fiji until it was brought there by Europeans. 

In New Guinea, malignant tumours are equally rare. " For nine and 
a half years," says MacGregor, " I never saw a case in British New Guinea ; 
but at the end of that time there occurred an example of sarcoma of the 
tibia in a Papuan, who had for seven or eight years lived practically a 
European life, eating tinned Australian meat daily " etc. Malarial and 
venereal affections are very prevalent, and tuberculosis as well, lupus 
exedens also is common. 

In Borneo, cancer is quite as rare as in New Guinea. Pagel, 3 who 
practised in North Bornea for ten years, never saw a single case ; and 
Nieuwenhuis 4 had a similar experience. 

In Java and Sumatra it is just the same, a single example of a malig- 
nant tumour in a native being esteemed a great rarity (Kohlbriigge, Van 
der Burg etc.). 

In the Philippine Islands similar conditions prevail. Thus, of 631 
deaths among natives at Manila, 5 during the month of February, 1903, 
in which the causation was known, there was not a single instance of 
cancer, but 78 deaths were due to phthisis. 



General Survey of the Distribution of Cancer in Africa. 

No part of the world is believed to be so comparatively immune from 
cancerous diseases as Africa, and this applies to nearly all parts of the 
continent, but especially to its northern parts Egypt, Tunis, Algeria etc. 

A few years ago, desiring to ascertain the actual incidence of the 
disease in Egypt, I wrote to Dr. Engel, of Cairo, who is in charge of the 
Egyptian vital statistics, and he kindly supplied me with the following 
data : 

Of 19,529 deaths among natives of Cairo during 1891, only 19 were 
due to cancer (females 10, males 9), or 1 in 1,028. In England, during 
the same year, the proportion of cancer deaths was 1 in 29. 

Of 12,950 patients at the Kasr-el-Aini Hospital during the years 

1 Colonial Report, No. 19, 1902, p. 141. 

2 Lancet, vol. ii., 1900, p. 1057. 

3 Deutsch. med. Woch., October 17, 1901. 

4 Janus, 1899. 

5 Journal of Tropical Medicine, July 1, 1904, p. 208. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 43 

1889-1891, only 77 were affected with cancer, or 0-6 per cent. ; whereas, 
in London general hospitals at about the same period, I have ascertained 
that the proportion of cancer patients was 3-5 per cent. 

From these data, it appears that the reputation of Egypt for com- 
parative immunity from cancer is well founded. 

In this Dr. F. C. Madden, of Cairo, concurs. Thus he says : l " The 
consensus of opinion among medical men in Egypt is, that cancer is never 
found either in male or female, among the black races of that country. 
These include the Berberines and the Sudanese, who are all Mussulmans, 
and live almost entirely upon vegetarian diet. Cancer is fairly common, 
however, among the Arabs and Copts, who live and eat somewhat after 
the manner of Europeans." 

Griesinger states that he never met with a single case of cancer of the 
stomach, during many years' practice in Egypt. 

Insanity is phenomenally rare in Egypt, but there is a fair amount 
of tuberculous disease, including phthisis ; while malarial and venereal 
affections, including syphilis, are very common, " condylomata flourishing 
with tropical luxuriance " (Madden). 

Several authors have called attention to the rarity of malignant 
tumours among the natives of Algeria (Legrain, Kirmisson etc.), and 
have ascribed this comparative immunity to their abstinence from 
animal food and intoxicating drinks. 

The official statistics for Algeria 2 relate only to the towns, which 
comprise for the most part a large European element, as at Algiers, 
where the cancer death-rate in 1895, was 56 per 100,000 living ; but at 
Oran, where there are but few Europeans, the cancer death-rate was 
only 1-3 ; while at Biskra, with nearly 8,000 inhabitants, at Batna, with 
over 6,000, at Mostaganem, with over 16,000 inhabitants, not a single 
death from cancer was registered ; and at Guelma, with over 7,000 inhabi- 
tants, there was only one death from cancer. 

Many travellers have commented on the rarity of cancer in Tunisia ; 
and, according to Behold and Tiriant, it is not met with among the 
aborigines. 

With regard to the incidence of cancerous diseases in Morocco, I am 
indebted to the late Ernest Hart for the following valuable information. 
In answer to my letter of inquiry, he very kindly wrote to Dr. Terry, of 
Tangiers, who replied as follows : " Cancers, sarcomas etc., do not seem 
to be very prevalent. At any rate, the number of cases met with, as 
compared with other diseases, show that they are of less frequent occur- 
rence than in England. Among the inhabitants, who are of mixed Arab 
and native blood, I have seen cancers of the female breast, uterus, and 
of the tongue, as well as sarcomatous growths in various parts of the 
body." 

In Madeira and the Canary Islands cancer is said to be oftener met 
with than in North Africa (Behla) ; but Dr. J. Goldschmidt 3 has found 
that the disease is decidedly rare in the former island. 

1 British Medical Journal, vol. ii., 1902, p. 730. 

2 Statistique sanitaire des villes de France et d' Algerie pendant I'annee 1895, p. 114. 

3 Deutsche med. Woch., July 10, 1902. 



44 THE NATURAL HISTORY OF CANCER 

Among the natives of the Sudan seen by Dr. A. Balfour 1 at Khartoum, 
instances of carcinoma and sarcoma were occasionally met with. 

During his visit to Somaliland and Erythrea a few years ago, Fiaschi 2 
was struck with the remarkable absence of malignant tumours among 
the crowds who flocked to his clinic, although tuberculous and syphilitic 
affections were common. 

We have no recent information as to the incidence of these maladies 
in Abyssinia, but by the older writers they are said to be commoner in 
this country than in any other part of Africa. Dr. C. Singer, 3 who lately 
travelled through the south-west of Abyssinia, describes goitre and Graves' 
disease as being common ; and in a Galla he saw a large osteoma of the 
ribs, but he makes no mention of having seen a single instance of cancer. 

On the West Coast malignant tumours are very .rare among the 
aborigines. Malaria is exceedingly prevalent, but tubercle is rare, except 
among natives who have acquired semi-civilized habits. The records of 
native patients treated at Bathurst, in Gambia, for many years contain 
not a single entry under cancer ; and Dr. Forde, 4 during nine years' 
practice there, never saw a single case. 

During the year 1903, of 9,068 patients (in 591, out 8,477) treated 
at Government hospitals etc., not a single instance of malignant or any 
other tumour was met with, throughout the Gambia colony. 

In the Gold Coast colonies cancer is very rare, as it is also in Ashanti. 
During ten years' practice in the latter country, Dr. Henderson 5 never 
saw a single case. 

According to Bornier, 6 cancer is never seen among the Senegal negroes. 
During fourteen years' practice at Lagos, Dr. O. Johnson ? saw but five 
instances in natives, and these had all lived for many years a semi- 
civilized life, eating meat etc., like Europeans. Plehn met with only a 
few cases of sarcoma among the natives of the Cameroons. In British 
Nigeria, during 1900, 8 5,690 natives were treated at the various hospitals 
and dispensaries, but not a single death from malignant - tumour is 
recorded. 

In Uganda, that Central African community where the indigenous 
civilization attained its maximum, malignant tumours, although very 
much less common than among Europeans, are said to be by no means 
rare. At Dr. Cook's hospital at Mengo, 9 cases of carcinoma of the lip, 
oesophagus, breast, uterus, intestine etc., have been under treatment ; 
as well as cases of chondro-sarcoma of the parotid, sarcoma of the jaws, 
melanosis etc. Uterine myomata and ovarian cystomata are also fairly 
common, as well as various other non-malignant tumours, such as lipoma, 
fibroma, enchondroma, osteoma, nsevus, sebaceous and dermoid cysts. 

Although Uganda has a cool climate for Equatorial Africa, and lies 

1 Journal of Tropical Medicine, April 15, 1904, p. 118. 

British Medical Journal, 1897, vol. i., p. 687. 
3 Journal of Tropical Medicine, January 16, 1905, p. 17. 

Report on Cancer in British Colonies, 1905 

5 Ibid., 1905. 

6 Path. Compare, etc., 1889, p. 254. 

7 Lancet, vol. ii., 1900, p. 1057. 

Colonial Report, No. 19, 1902, p. 190. 

9 Journal of Tropical Medicine, June 1, 1901, p. 173. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 45 

high, its mean elevation being 4,000 feet above the sea-level, malaria is 
exceedingly prevalent, constituting nearly 25 per cent, of all the cases 
treated. Syphilis also is rampant, 10-5 per cent, of the admissions being 
for this disease ; while tuberculous maladies account only for 4 per cent. 
The country is hilly, and many of the people are affected with goitre and 
albinism. The natives are clean, intelligent, and " splendidly developed 
physically." Their staple food comprises plantains, bananas, and sweet 
potatoes, while banana wine is extensively consumed ; but meat can 
seldom be obtained. In other parts of Central Africa cancer is decidedly 
very rare. 1 Thus, Dr. Scott, of the Zomba Mission, who has been in the 
country for fifteen years, has never seen a single case ; and Dr. Morris, 
formerly of the Blantyre Mission, in four years' work saw only a single 
case. In like manner, Dr. Old, during four years' work there, met with 
only two cases of malignant disease, while Dr. Hearsey's 2 testimony is 
to the same effect. 

Dr. A. R. Sieveking, now of Bristol, who practised for several years 
among the natives of Masailand, informs me that he never saw a single 
example of malignant tumour among them, although this part of the 
country was well stocked with big game, which formed an important part 
of the natives' food when they could get it. 

Among the natives of the Nyassaland plateau, Dr. Kellett-Smith 3 
found that all kinds of malignant tumours were so rare "as to be prac- 
tically unknown." Although all scars tended to become keloid, yet 
these keloids never took on malignant properties. Syphilis seemed to be 
incapable of permanently establishing itself among the natives. Generally 
speaking, in British Central Africa malignant tumours are decidedly rare. 

In Mauritius and the Seychelles cancer is also rare. At the former 
place, in 1903, 67 cases of cancer were met with among 21.356 hospital 
patients ; 4 at the latter place, of 219 hospital patients, only 2 had cancer 
(both of the stomach). In the mixed population of St. Helena cancer is 
not uncommon. 

Livingstone 5 speaks of cancer as being absent from theBarotze country, 
and among the Bakwains, although the latter are prone to fatty and 
fibrous tumours. 

The natives of Mashonaland and Bechuanaland are said to be equally 
exempt. 

In Basutoland malignant tumours are rare. 6 At the Leribe Hospital, 
3,128 natives were treated in 1900, of whom 4 had malignant and 25 non- 
malignant tumours. Of 4,684 patients at the Maseru Dispensary in the 
same year, 2 had cancer and 44 various non-malignant tumours, including 
6 cases of lipoma and 3 dermoid cysts. Of 2,679 natives treated at the 
Mafeking Hospital, 6 had cancer, 4 sarcoma, and 22 various non-malignant 
tumours ; and at Quthing, of 1,242 patients, 2 had cancer and 7 non- 
malignant tumours (enchondroma, 3 ; fibroma, 2 ; lipoma, 2). 

1 Report on Cancer in British Colonies, 1905. 

2 British Medical Journal, 1906, vol. ii., p. 1562. 

3 Liverpool Med.-Chir. Journal. 1901, vol. xxi., p. 46. 

4 Report on Cancer in British Colonies, 1905. 

5 " Missionary Travels in South Africa," etc., pp. 127, 504. 

6 Colonial Report, No. 19, 1902, p. 25. 



46 THE NATURAL HISTORY OF CANCER 

Cancer is very rare among the natives of Natal, 1 especially among those 
of Bantu origin, for out of a population of 86,000, with a general death- 
rate of 19 per 1,000, only one death was ascribed to this cause in 1903. 

An example of a large sarcoma of the lumbo-sacral region in a Zulu, 
aged thirty, has lately been described by Dr. H. Goodman, of Johannes- 
burg. 2 

According to Hawes, 3 cancer is very rare among the Hottentots. He 
has, however, met with three instances in natives of this race, one of 
whom had lived for many years as a servant in an English family. 

Among the Boers and Europeans living in South Africa, who are 
large flesh-eaters, malignant tumours are common ; but among the 
natives, who are mainly vegetarians, these tumours are so rare as to be 
almost unknown. 



General Survey of the Distribution of Cancer in America. 

Owing to the fact that compulsory death registration in the United 
States is confined to a limited area (comprising a population of about 
29,000,000) ; while for the rest of the country (comprising a population 
of over 47,000,000), the statisticians have to depend for their information 
on the data supplied by the " enumerators," who as we are told in the 
introduction of the official report 4 often fail to make inquiry as to the 
cause of death, or, indeed, to make any return of deaths at all, the official 
reports compare unfavourably, so far as accuracy and reliability are 
concerned, with corresponding European publications. 

In consequence of this unsatisfactory state of affairs, we have two 
estimates as to the incidence of cancer in the United States, the one 
based on the returns for the whole country, the other on the more reliable 
data for the " registration area." 

According to the former, the cancer 5 death-rate in 1900, was 43 per 
100,000 living, being 1 in 2,309 of the total population, or 1 in 31 of the 
total deaths. 

According to the latter, the cancer death-rate 6 was 60 for the same 
year, being 1 in 1,665 of the total population, or 1 in 29 of the total 
deaths. 

Of these two estimates, the latter is the more reliable ; but my im- 
pression is that both of them understate the incidence of the disease, 
which is, I expect, but little less in the United States than in Europe. 

In the " registration area," the death-rates from the disease in the 
various states were as follows : Maine, 83 ; Vermont, 81 ; Columbia, 71 ; 
New Hampshire, 66 ; Massachusetts, 66 ; Rhode Island, 62 ; New York, 
61 ; Connecticut, 61 ; Michigan, 58 ; and New Jersey, 50. 

In the United States, as in Europe, Australia etc., the cancer mortality 
is increasing. 

For the chief towns the rates were as follows: San Francisco, 112 

1 Report of Medical Officer of Health for Natal for the year 1903. 

2 Transvaal Medical Journal, May, 1906, p. 319. 

3 Bartholomew's Hospital Reports, vol. xli., 1906, p. 161. 

4 Twelfth Census Report of the United States, 1900, vol. iii., part i. 

5 Comprises cancer and tumour. 6 Without tumour. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE 47 

(1900) ; Boston, 76 (1898) ; Philadelphia, 73 (1900) ; Baltimore, 69 (1904) ; 
New York, 64 (1900) ; New Orleans, 64 (1898) ; Chicago, 63 (1900) ; Buffalo, 
53 (1899) etc. 

The returns indicate greater prevalence of the disease in rural (death- 
rate 71), than in urban districts (death-rate 65) ; but, for the reasons 
above mentioned, too much importance should not be attached to these 
estimates. 

Another source of fallacy in the United States vital statistics is that 
" cancer and tumour " are " considered together, as it is found impossible 
accurately to distinguish them, as they are commonly reported." * 

In all parts of British North America cancer is fairly common among 
the whites, probably about as common as in the United States, but I 
have been unable to meet with any satisfactory recent statistics. Among 
the aborigines of Canada, Landry 2 (1861) found that cancer was exceed- 
ingly rare, and it is still very infrequent. 

Of 3,275 necropsies at the chief Montreal hospitals (up to 1904), 275, 
or 1 in 11-9, were for cancer. This nearly corresponds with the ratio in 
German hospitals, which has been estimated at 1 in 12 ; and the Guy's 
Hospital records show, that 1 in 8 of all necropsies there are for cancer. 

In the province of Ontario there were 1,055 deaths from malignant 
tumours, in 1900. 

For some of the chief towns, the cancer death-rates per 100,000 living 
in 1891, were as follows : Halifax, 54 ; Quebec, 42 ; Montreal, 39 ; Toronto, 
36 ; and St. John, 15. For Victoria (British Columbia) the rate was 110 
in 1896. 

In Mexico cancer is fairly common among those of European descent, 
who live in the high, cool regions, and even the semi-civilized natives and 
half-castes are affected ; 3 but, according to Jourdanet, it is almost un- 
known in the low-lying hot regions. 

In the Central American communities the disease is rare, the Guate- 
malan cancer death-rate for 1894, being only 4 ; and in British Honduras 
the malady is equally rare. 

In the Bermudas* malignant tumours are met with among those of 
white, as well as those of coloured descent ; thus, of 423 deaths in 1900, 
13 were due to this cause, or 1 in 33. 

Of 145 deaths among whites, 8 (males 2, females 6) were due to cancer, 
or 1 in 18 ; of 278 deaths among the coloured, 5 (males 1, females 4) were 
due to this disease, or 1 in 56. 

In the Bahamas, 5 with a population of 54,709 (mostly coloured), and 
a general mortality of 1,231, during the year 1900, there was only one 
death from cancer. 

Generally speaking, cancer is decidedly rare in the West Indies, but 
more than half a century ago L. Young had noted occasional examples 
of it. Thus he says : 6 " Among West Indian negresses malignant disease 
of the uterus and mamma is of very rare occurrence, and even those 

Twelfth Census Report of United States, 1900, vol. iii., part i., p. clxixi. 

Bull, de la Soc. d'Anthropologie, t. ii., p. 16. 

Rodman, " International Text-Book of Surgery." vol. ii., 1900. p. 731. 

Colonial Report, No. 19, 1902. 6 Ibid., p. 20. 

Cited by Astley Cooper in his " Anatomy of the Breast," etc., 1840. 



48 THE NATURAL HISTORY OF CANCER 

cases which I have witnessed in this class of people have been among the 
better orders of them, whose habits of living have been assimilated to 
those of Europeans." 

In Jamaica the death-rate from this cause in 1888, was nearly 12 per 
100,000 living, which in 1905 had increased to 19. The phthisis death- 
rate for the island amounted to 155 in 1903, and the average for 1895- 
1904 has been 160. 

Of 1,317 deaths in the hospitals of Trinidad and Tobago 1 during 1900, 
13 were due to malignant tumours, or about 1 in 102. The localities 
affected were the female genitalia in 5 cases, the liver in 3 cases, and 1 
each of the mamma, stomach, and larynx. Fifty-five cases of non- 
malignant tumours were also treated at these hospitals, including 23 
uterine myomata and 2 ovarian cysts. 

In the various hospitals of Grenada, 2 in 1900, 490 patients were under 
treatment, of whom 8 had malignant tumours, or 1 in 62. 

At St. Lucia, 3 of 2,810 hospital patients, with 159 deaths, in 1900, 
5 were due to cancer, or 1 in 32 of the deaths. Twenty- two patients were 
treated for non-malignant tumours during the same year. 

Of 30,856 natives of St. Kitts,* 899 died during 1900, malignant 
tumours being the cause of death in 4. Thus, the cancer death-rate per 
100,000 living was nearly 13, or 1 in 225 of the total deaths. 

Among the 2,463 Europeans, there was not a single death from this 
cause during the year. 

At Nevis, 5 with a population of 14,520 natives, of whom 294 died 
during the year, there was not a single death from cancer. 

In Anguilla, 6 with a native population of 4,424 and 55 deaths, only 
one death from cancer occurred during the year, the rectum being the 
part attacked. With regard to this case, the medical officer says in his 
report : "A few deaths from cancer are recorded as having occurred 
among the black population prior to my arrival in the island ; but, 
during my three years' residence here, I have only seen this one case of 
cancer among the blacks. The whites are, however, fairly often attacked, 
especially with ulcerated forms of cutaneous cancer." Thus, of 32 deaths 
among whites during the period 1892-1900, 5 were due to cancer ; where- 
as, of 479 deaths among the blacks during the same period, only 2 were 
due to this cause. Phthisis and malaria are common in the island. 

In the tropical parts of South America cancer is decidedly rare among 
the natives. 

In British Guiana? of 148,221 patients treated at the public hospitals 
during the year 1903-1904, only 105 had malignant tumours ; and there 
were 93 instances of non-malignant tumours. Of 1,556 deaths in these 
hospitals during the same year, 27 were due to malignant disease. Malaria 
and tubercle are very prevalent, the latter malady causing 13-9 per cent, 
of all deaths. 

Spitzly, 8 during a sojourn of eight years in the Surinam district of 

1 Colonial Report, No. 19, 1902. 2 Ibid 

I Ibid. * Ibid. s Ibid 6 Ibid ] 

7 Report of the Medical Department of British Guiana, 1903-1904. 

8 British MedicalJournal, vol. i., 1902, p. 16. 



GEOGRAPHICAL DISTRIBUTION AND INCIDENCE ; 49 

Dutch Guiana, found that the various forms of malignant tumours were 
not very common there. He met with the following cases : cancer of 
the tongue in an escaped Cabyle convict, malignant disease of the glands 
of the neck in a Guiana-born Jew of fifty, melanotic sarcoma of the 
external auditory meatus in a coloured man from Niekerie, cancer of 
the tongue in a Chinaman, several cases of mammary cancer in Creole 
women, malignant disease of the bladder in a middle-aged coloured native 
of Paramaribo who was a prison warder, several cases of cancer of the 
lip and penis in coloured people who had always lived in Surinam, etc. 
Malaria is very prevalent in Dutch as in British Guiana. 

Cancer is rare in Brazil, especially in the Equatorial regions, the death- 
rate from this cause for 1903, being only 4 per 100,000 living (Sodre).i 
The uterus is the part oftenest affected, gastro-intestinal localizations 
being comparatively rare. The maximum of frequency is attained in 
the province of Rio Grande do Sul. For Rio di Janeiro, with its popula- 
tion of 850,000, the cancer death-rate was about 26 per 100,000 living in 
1904, the tubercle mortality being 287, that for malaria 70, and the 
general death-rate from all causes 2,050. 

In Uruguay cancer is comparatively common, the death-rate from 
this cause in 1897, being 47, or 3-28 per cent, of the total deaths, and 
tubercle is prevalent. 

In Argentina cancer is also fairly common, especially in Buenos Aires, 
where the rate in 1900, was 91. In the province of Tucuman, the cancer 
death-rate for 1898, was only 10. 

1 Brazil Med. (Rio di Janeiro), 1904, vol. xviii., p. 229. 



CHAPTER III 

THE INCREASE OF CANCER, AND ITS CONCOMITANTS 
Preliminary Review. 

IN the course of organic evolution some types of disease, like species, 
have diminished and become extinct, while others have increased and 
become more prevalent. In comparatively recent times typhus fever, 
leprosy, malaria, scurvy, plague, and dysentery have almost or quite 
disappeared from our country ; small-pox and other zymotic diseases 
have greatly diminished ; while phthisis and tuberculous affections are 
decidedly on the wane. 

On the other hand, a small group of maladies, of which cancer is the 
chief, has steadily increased ; and this in spite of progressive diminution 
in the general death-rate, with other signs of material prosperity. Of 
the other members of this group, insanity, suicide, alcoholism, diabetes, 
and diseases of the circulatory system, are the chief ; while to these 'may 
be added premature births and congenital deformities. 

In all modern communities, where the occidental type of civilization 
prevails of which the chief characteristics are industrialism and urbaniza- 
tion, with great increase and widespread diffusion of material prosperity 
a similar tendency is noticeable, especially as regards cancer, the inci- 
dence of this malady having doubled in frequency in periods of from 
twenty to thirty years, the annual increment of increase averaging from 
3 to 5 per cent. 

This tendency seems to be of comparatively recent origin. At any 
rate, cancer is a disease of great antiquity, which is known to have 
existed from the most remote times of which we have any record. The 
" Papyrus Ebers," which is believed to have been written about 1550 B.C., 
contains a short section on malignant and other tumours, from which it 
may be inferred that the cardinal features of these maladies were then 
well recognized. In the works of Hippocrates, who is believed to have 
flourished during the latter part of the fifth century B.C., malignant and 
other tumours are referred to ; but, in the somewhat detailed enumeration 
of the various maladies prone to occur at the different periods of life, 
which is embodied in the " Aphorisms," no mention is made of cancer. 
From this omission, and from the comparative paucity of the references 
to cancer in the Hippocratic writings, I conclude this affection must then 
have been comparatively rare. 

We have singularly little trustworthy information as to the pre- 
valence of cancer in this country during the Middle Ages and at earlier 

50 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 51 

periods ; but from such indications as are available, it seems likely that 
the malady then was of much less frequent occurrence than in modern 
times. The exceptionally well-kept registers of Market Deeping (Lin- 
colnshire), during the years 1711 to 1723, in a total of 387 deaths, show 
only two from cancer (one male and one female). 1 

A unique statistical study of cancer incidence, during the whole of 
the nineteenth century, has been made by Ekblom 2 for the small Swedish 
town of Fellingsbro. Taking the averages for the first and last decennial 
periods of the century, he found that the cancer death-rate had increased 
from 2-1 per 100,000 living in the former period, to 118 in the latter. 

The data derived from the long experience of the Scottish Widows' 
Life Assurance Fund, 3 are also of value in this connexion. Thus, the 
proportion of deaths due to cancer, to the total mortality among the 
males assured since 1815, has shown the following increases : 

Per Cent. 
1815 to 1844 . . . . . 0'93 



1845 
1859 

1867 
1874 
1881 
1888 



1858 
1866 
1873 
1880 
1887 
1894 



T79 
3-00 
4-56 
4'93 
5'44 
6'88 



The experience of the chief German Life Assurance Company, as 
lately reported by Juliusberger, 4 is to the same effect. Thus, the cancer 
mortality among males, in the period 1885-1889, amounted to 3-7 per 
cent, of the total deaths, and among females to 114 per cent. ; whereas, 
for the period 1889-1895, the corresponding ratios were 11-4 for men 
and 12-9 for women. 

England and Wales. 

Statistical Summary. 

In this country the civil registration of births, deaths, and marriages 
came into operation in 1837 ; and the first annual report of the Registrar- 
General (for the year ending June, 1838) was published in 1839, the cancer 
death-rate then being 166 per million living. In the sixty-eighth of these 
reports for 1905 this rate had increased to 885, or more than fivefold. 

In the very earliest years of registration, before the enumerating 
machinery had been perfected, the data elicited may have left something 
to be desired. We will therefore commence our study with the year 
1840, when the national statistics, under the able direction of William 
Farr, had already acquired well-deserved reputation for reliability. 

In that year 2,786 persons died of malignant disease in England and 
Wales, the proportion being 1 in 5,646 of the total population, 1 in 129 
of the total mortality, or 177 per million living. 

In 1905 the deaths due to this cause numbered 30,221, being 1 in 
1,131 of the total population, 1 in 17 of the total mortality, or 885 per 
million living. 

1 British Medical Journal, vol. i., 1896, p. 915 (Newman). 

2 Htjgeia, January, 1902. 

3 Causes of death among the assured in the Scottish Widows' Fund (C. Muirhead), 
1902, Edin. Appendix. * Zeite. f. Krebsforschung, 1905. 

42 



52 THE NATURAL HISTORY OF CANCER 

In this respect, the position occupied by cancer is unique, for no 
other malady can show such a great increase. Thus, whatever the 
etiological factors of cancer may be, it is evident that they are not con- 
stant in action ; and, if capable of exacerbation in some circumstances, 
they may be amenable to diminution in others. In this direction, it 
seems to me, we may reasonably hope to discover indications that will 
show us how to check the increase of the malady, and even enable us 
eventually to greatly reduce its mortality. 

I believe that the tendency to cancer may be increased by unsuitable 
modes of living, and vice versa- We must therefore seek out those 
conditions which favour its development ; and, by avoiding them, we shall 
then be able to effect our object. In my opinion, it is only by progress 
along such lines, that the prevention of cancer is ever likely to be effected. 

In further illustration of this subject, I have compiled the following 
table (see p. 53), which shows the increments of increase during the long 
succession of years. 

The Reality of the Increase. 

With these figures before us, and all that they imply, there can be no 
doubt as to the reality of the increase in the cancer mortality. Yet this 
has been called in question. The earliest objectors ascribed the registered 
augmentation to mere increase of population ; but the futility of this is 
demonstrated by the fact that, while the population barely doubled 
(1850-1905), the cancer mortality increased more than sixfold. 

Next the attempt was made to explain the increase as due to the 
average age of the population having advanced, and the consequent 
liability of greater numbers. To this the answer is that the saving of 
life in modern times has mainly been confined to the precancerous years 
^ of existence, the death-rates of males over thirty-five and of females over 
forty-five having remained almost stationary, while the numbers attaining 
old age have decreased. Hence only an infinitesimal fraction of the 
increased cancer mortality can be thus accounted for. Moreover, an 
increase in the cancer mortality is by no means a necessary corollary of 
the survival of augmented numbers to the cancer age, as the Irish mor- 
tality statistics show. 

Another objection to the reality of the increase in cancer has been 
raised by Dr. A. Newsholme 1 and his followers. They maintain that the 
registered increase is only apparent, being due to improved diagnosis 
and more careful death certification. There is, however, far too much 
uniformity in the steadily progressive increments of increase, during the 
long succession of years, to furnish any warrant for such a suggestion ; 
while, taken in its entirety, the increase is so enormous as to make this 
explanation seem quite far-fetched. 

Moreover, if improved diagnosis and death certification have caused 
additions to the cancer total which I do not deny these same condi- 
tions have also caused subtractions from it. Thus, as the Registrar- 
General tells us in his fifty-fifth report, even up to the year 1880 such 
common diseases as " fibroid tumour," " polypus," and " lupus," were 
1 Proceedings of the Royal Society, 1893, vol. liv., p. 209. 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 53 



TABLE SHOWING THE PREVALENCE OF CANCER AND ITS INCREASE 
IN ENGLAND AND WALES. 



Year. 


Total Popula- 
tion. 


Total 
Deaths. 


Cancer 
Deaths. 


Cancer Death- 
Rate per Mil- 
lion Living. 


Proportion to 
Population. 


Proportion 
to Total 
Deaths. 


1840 


15,730,813 


359.687 


2786 


177 


1 to 5646 


1 to 129 


1850 


17,773,324 


368,995 


4966 


279 


1 3579 


1 74 


1855 


18,829,000 


426,646 


6016 


319 


1 3129 


1 70 


1860 


19,902,713 


422,721 


6827 


343 


1 2915 


1 62 


1865 


21,145,151 


490,909 


7922 


372 


1 2670 


1 62 


1870 


22,501,316 


515,329 


9530 


424 


1 2361 


1 54 


1875 


24,045,385 


546,453 


11,336 


471 


1 2121 


1 48 


1880 


25,714,288 


528,624 


13,210 


502 


1 1946 


.1 40 


1881 


25,974,439 


491,937 


13,542 


520 


1 1918 


1 36 


1882 


26,413,861 


516,654 


14,057 


532 


1 1879 


1 36 


1883 


26,770,744 


522,997 


14,614 


546 


1 1763 


1 35 


1884 


26,922,192 


530,828 


15,192 


564 


1 1772 


1 35 


1885 


27,220,706 


522,750 


15,560 


572 


1 1749 


1 33 


1886 


27,522,532 


537,276 


16,243 


590 


1 1694 


1 33 


1887 
1888 


27,827,706 
28,136,258 


530,758 
510,971 


17,113 

t 

17',506 


615 
621 


1 1626 
1 1607 


1 31 
1 29 


1889 


28,448,239 


518,353 


18,654 


656 


1 1525 


1 30 


1890 


28,762,287 


562,248 


19,433 


676 


1 1480 


1 28 


1891 


29,081,047 


587,925 


20,117 


692 


1 1445 


1 29 


1892 


29,405,054 


559,684 


20,353 


690 


1 1445 


1 27 


1893 
1894 


29,731,100 
30,060,763 


569,958 

498,827 


21,135 
21,422 


711 
713 


1 1407 
1 1403 


1 27 
1 23 


1895 


30,383,047 


568,997 


22,945 


755 


1 1324 


1 24 


1896 


30,717,355 


526,727 


23,521 


764 


1 1306 


1 22 


1897 


31,055,355 


541,487 


24,443 


787 


1 1270 


1 22 


1898 


31,397*078 


552,141 


25,196 


802 


1 1246 


1 22 


1899 


31,907,762 


581,799 


26,325 


825 


1 1212 


1 22 


1900 


32,261,013 


587,830 


26,731 


828 


1 1207 


1 22 


1901 


32,621,263 


551,585 


27,487 


842 


1 1186 


1 20 


1902 


32,997,626 


535,538 


27,872 


844 


1 1183 


1 19 


1903 


33,378,338 


514,628 


29,089 


872 


1 1174 


1 17 


1904 


33,763,434 


549,784 


29.682 


877 


1 1138 


1 18 


1905 


34,152,977 


520,031 


30,221 


885 


1 1131 


1 17 

















54 



THE NATURAL HISTORY OF CANCER 



usually classed as cancer. In like manner, many other morbid states, 
formerly often regarded as cancerous, are now relegated to other cate- 
gories. It is hardly likely, then, that there is any validity in Newsholme's 
contention ; which, as I will now proceed to show, is in its main conten- 
tion a statistical sophism, based upon fallacious figures as well as upon 

fallacious reasoning. 

It is claimed that there has been no increase in the registered cancer 
mortality, for those parts of the body in which the disease is readily 
" accessible," and therefore presumably easy of diagnosis, such as the 
uterus, the mamma, the tongue, the mouth, etc. ; whereas, in '' inac- 
cessible " localities, such as the stomach, the liver, and the intestines, 
where diagnosis is presumed to be difficult, the increase is said to have 
been very marked. 

With regard to this, I have to remark that, although cancer is a disease 
which often presents great diagnostic difficulties in the earlier stages of 
its course ; yet, before the fatal termination is reached, such unmis- 
takable signs as to the real nature of the malady usually appear, as pre- 
clude the very frequent occurrence then of erroneous diagnosis. The 
very large proportion of mistaken diagnoses in the cases tabulated by the 
Cancer Research Fund, 1 by Bellinger etc., simply show that these were 
specially selected lots of difficult hospital cases ; and they cannot be 
regarded as being in any way typical of everyday experience. The 
diagnosis of advanced cancer is, indeed, generally not a very difficult 
matter, as compared with most diseases. 

In support of this " no increase " hypothesis, reference has been 
made to some data derived from the Scottish Widows' Life Assurance 
Society, and to mortality statistics of Frankfort ; but, as Dr. J. F. Payne 2 
has pointed out, these seem to be a very inadequate basis on which to 
raise such a superstructure. Before accepting any such conclusion, we 
must inquire whether similar results are arrived at in larger populations, 
and under more representative conditions. In the Report of the Registrar- 
General for 1889, a table is given with the object of determining this very 
question, by analysing a certain representative selection of the deaths 
from cancer, during the years 1868 and 1888 respectively. The results 
thus obtained with regard to localization may be epitomized as follows : 



MALES. 






FEMALES. 




Per 100 Deaths from Mali 


jnantDis 


ease. 


Per 100 Deaths from Malignant Dis 


jase. 


Stomach 


1868. 
35'3 


1888. 
24'0 


I 1868. 
Uterus . . . . . 38'0 


1888. 
31-4 


Liver 
Tongue and mouth 
Rectum . . 
Face . . i ! 
Intestine (ex rectum) 
All others 


12'0 

8-0 
7-8 
6'3 
4-0 
26-6 


14-9 

7'2 
8'9 
3'2 
6'6 
35'2 


Mamma . . . . . 24'2 
Stomach . . .. H'9 
Liver and gall-bladder 6'4 
Rectum . . . . 3'7 
Intestine (ex rectum) 2'1 
All others . . 13'7 


18'3 
1T9 
12-7 

4-8 
5'3 
15-6 




lOO'O 


100-0 


lOO'O 


lOO'O 



1 Sci. Hep., No. 2, part i., 1905, p. 18. 



2 Lancet, vol. ii., 1897, p. 765. 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 55 

The net result of this inquiry is to show, that the increase of the disease 
has not been confined to one or to some few parts of the body, but that 
it has involved them all. It is specially noticeable that cancer of the 
stomach, the chief representative of the " inaccessible " group, shows 
less relative augmentation, especially in males, than any other local 
variety of the disease ; and in both sexes, the death-rates from this form 
of cancer show less increase than those for cancer in general. Thus, in 
1868, the death-rate for cancer of the stomach per 1,000,000 living, thirty- 
five years old and upwards, was, for males, 283-65, and for females 193-45 ; 
whereas in 1888, the figures were, for males, 346-15, and for females 
277-75. Thus, the increase for males in the twenty years was 22 per 
cent., and for females 44 per cent. ; but, during the same period, the 
death-rate for cancer in general increased 50 per cent. 

If we compare modern statistics as to the site incidence of the disease, 
with older data collected by Marc d'Espine (Geneva, 1838-1855), and 
by Virchow (Wiirzbourg, 1852-1855), the localization ratios are seen 
to be very similar. Thus, d'Espine's statistics show 63-3 per cent, of 
digestive-system cancer (stomach, 45 ; liver etc., 12 ; intestines and 
rectum, 6-3); Virchow's 50-5 (stomach, 34-9; intestines, 8-1 ; liver etc., 7-5). 
With these the Registrar-General's data for 1900, may be contrasted, the 
total for the digestive system being 49 per cent, (stomach, 21-5 ; liver, 14-1 ; 
rectum, 7-1 ; intestines, 6-3). There is here no sign of any specially dis- 
proportionate increase of cancer of the digestive system ; and it is the 
same with the other chief local seats of the disease uterus 18-5 per 
cent. (Virchow), 15 (d'Espine), and 11-2 (Registrar-General, 1900) etc. 

So far, therefore, as these analyses go, Newsholme's postulates are 
shown to be untenable. Since the year 1897, Dr. Tatham has introduced 
into the Registrar-General's Annual Reports, a table showing the localiza- 
tion of the disease for each year. Analysis of these tables, for the years 
1897 and 1900 respectively, gives the following results : 



MALES. 


FEMALES. 


Per 100 Deaths from Malignant Disease. 


Per 100 Deaths from Malignant Disease. 




1897. 


1900. 




1897. 


1900. 


Stomach 


20' 6 


20-5 


Uterus . 


23-5 


22-5 


Liver 


14-2 


13-9 


Breast . 


15-5 


15-8 


Rectum . . . . i 8'6 


9-0 


Stomach . 


11-3 


13-8 


Tongue and mouth j 6'3 


6-8 


Liver 


13'2 


14-3 


Intestine (ex rectum) 


6'3 


7'0 


Rectum . 


5'2 


5'2 


(Esophagus 


5'7 


5'4 


Intestine (ex rectum,) 


5-2 


5'7 


Bladder .. 


3-3 


2-8 


Ovary 


1*7 


T7 


Jaws 


3-0 


23 


(Esophagus 


T4 


11 


Neck 
Pharynx, tonsils, etc. . 


2'7 
2'3 


2-3 
2-2 


Tongue and mouth 
Bladder .. 


11 

0-8 


0-6 
0'9 


Larynx and trachea 


1-8 


2-0 


Jaws 


0-6 


0-6 


Testis and penis 


1-5 


T5 


Neck 


0-6 


0'5 




76-3 


75-7 




82'3 


82'9 


All others 


23-7 


24-3 


All others 


17'7 


17-1 




100-0 


100-0 




100-0 


lOO'O 



56 THE NATURAL HISTORY OF CANCER 

The general tenour of these results, accords with that shown in the 
preceding analysis. The proportionate localization ratios show that there 
has been no special increase in the " inaccessible " manifestations of the 
disease ; and this is very noticeable in such organs as the .stomach and 
liver, which comprise the great majority of this form of the disease. 
Here again, then, Newsholme's hypothesis is shown to be devoid of solid 
foundation. 

Further confutation of this hypothesis comes from the work of 
Dr. Claud Muirhead, the medical officer of the Scottish Widows' Life 
Assurance Society, 1 who found that the cancer death-rate among the 
assured males, was nearly twice as great in 1881-1890, as it was in 1861- 
1870. In a society of this kind, whose members can command the 
services of highly skilled medical men, it is hardly likely that such a great 
increase could be due to improved diagnosis and death certification, 
especially as every death, where there was a suspicion of cancer, was 
carefully investigated. " I think it is evident," says Muirhead, " that 
the theory that this large increase was wholly or even largely caused 
by sudden increase of diagnostic skill among the class of medical men 
who certify causes of death to this society, is untenable." This conten- 
tion is fully endorsed by an examination of the localization ratios in 512 
fatal cases, in which the exact site of the disease was specified. From 
this it appears that the deaths from malignant disease of " inaccessible " 
parts (stomach, liver, etc.) decreased by 7-70 per cent, from 1874-1880 to 
1888-1894 ; and the results thus obtained by comparing the percentages 
of actual deaths, were entirely in accord with those arrived at by com- 
paring the respective death-rates. Thus the reality of the increase of the 
disease among the members of this society, was clearly demonstrated. 

I find it quite impossible to believe that anything like the great 
increase in the cancer mortality, indicated by the foregoing table, can be 
accounted for by improved diagnosis, by more accurate death certifica- 
tion, by changes in classification, or by alterations in the age and sex 
distribution of the population etc. 

In this connexion, some valuable evidence has lately been adduced 
by Dr. F. L. Hoffman, statistician to the Prudential Insurance Com- 
pany of America.2 He has found, for instance, that in Rhode Island, 
during the period from 1876-1880 to 1896-1900, cancer of the breast 
among women increased by 115 per cent. ; and in the city of Philadelphia 
the same malady, during the period from 1861-1865 to 1896-1900, in- 
creased 179 per cent. Here there can be no question as to the disturbing 
influence of sex diversities, nor of " inaccessible " localization etc. 
Neither is there any known marked alteration in the age distribution 
of these women, that would account for this increase. 

Another consideration of similar import is, that the increased cancer 
mortality has been diffused all over the country, instead of being limited 
to certain areas only ; so that those localities which formerly had the 
highest, lowest, and average cancer death-rates, still preserve their dis- 

1 " The Causes of Death among the Assured in the Scottish Widows' Life Assurance 
Society," p. 13. Edinburgh, 1902. 

2 Journal of the American Medical Association, October 19, 1901, p. 101. 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 57 

tinction in this respect, although the cancer mortality has everywhere 
augmented. Taking all these facts into consideration, there can, then, 
be no doubt as to the reality of the increase in the cancer mortality. 
When, therefore, Dr. Bashford says : * " There is nothing in the statistical 
investigations of the Imperial Cancer Research Fund, which points to an 
actual increase in the death-rate from cancer :" I reply, that investigations 
conceived and executed in such an exceedingly faulty and imperfect 
manner, as those referred to, could not be expected to yield results having 
any scientific validity. 



The Disproportionate Increase among Men. 

The Registrar-General's Annual Reports show that more women die 
from malignant disease than men, and this has been the case ever since 
these reports were first issued (1839). 2 In the year 1900, this disease was 
fatal to 16,246 females and to 10,475 males. For females the death- 
rate was 975 per 1,000,000 living of that sex, for males 672. In other 
words, 1 in 15 of all men, and 1 in 9 of all women, thirty-five years old 
and upwards, eventually died of cancer. The cancer mortality among 
males in that year, exceeded the decennial average for the male sex by 
16 per cent. ; and among females by 10 per cent. Attention is thus 
drawn to the remarkable fact, that the increasing cancer mortality is 
affecting, and for many years has affected, males to a much greater 
extent than females. The difference between the sexes in respect to 
their proclivity to malignant disease, has thus been steadily diminishing 
ever since 1850, as is shown by the following table : 

TABLE SHOWING THE INCREASE OF MALIGNANT DISEASE AMONG 
MALES AND FEMALES PER MILLION LIVING. 





Period. 




Male Cancer Death-rate. 


Female Cancer Death- e e _. 
rate. 


Ratio. 










i 




1851 t 


o 1860 




195 


434 It 


o2'2 


1861 


1870 




244 


523 1 


, 2-1 


1871 


1880 




315 


622 1 


, T9 


1881 


1890 




430 


739 1 


, T7 


1891 


1900 




597 


903 1 


, 1'5 


1901 


1905 




723 


997 1 

1 


, 1-3 



It thus appears that, although there has been a great increase of 
malignant disease in both sexes during the last half -century, and although 
at the present time more women are affected than men, yet the malady 
has augmented much more rapidly among the latter than among the 
former. Moreover, it is noticeable that the average age of English 
women is higher than that of men, so that the death-rates, as given 
above, are unduly favourable to the female sex. 

It seems likely, if this disproportionate increase of cancer among 
males is not checked, that the disease will soon be as prevalent among 

1 Set. Hep., No. 2. part i., 1905. 

2 In 1838. 620 males and 1,828 females died of cancer, the respective death-rates being 
84 for males and 240 for females, or 1 male to 2'74 females. 



58 THE NATURAL HISTORY OF CANCER 

men as among women ; or the comparative proclivity of the sexes in the 
respect may be reversed, 1 as has already happened in a few countries 
e.g., Australia, New Zealand etc. 

The greater prevalence of malignant disease among women, is entirely 
due to the frequency with which, in them, the mammae and uterus are 
affected, the corresponding structures in males very rarely originating 
the disease ; while, in all other localities, the male liability is the greater. 

Here it may be noted that the comparative proclivity of women to 
non-malignant tumours and cysts, is even more considerable than it is 
to cancer ; and this also arises from the fact that, in them, the reproductive 
organs, especially the uterus and ovaries, very frequently originate 
tumours of this kind, whereas the corresponding male organs are seldom 
affected. 

Another point worthy of notice in this connexion is that, for both 
sexes, the percentage of cancer deaths at ages above forty-five is greater 
than it used to be, the disproportionate increase in the male cancer 
mortality being mainly due to excessive incidence of the disease at 
comparatively advanced ages. 

If now we ask, What is the cause of this disproportionate increase of 
cancer among men ? Newsholme, De Bovis, and others reply : There 
has been no real increase, but the apparent augmentation is due to 
improved diagnosis and death certification, owing to the majority of 
cancers in men being of the " inaccessible " variety, which is difficult to 
discriminate. As I have, in the foregoing remarks, fully exposed the 
fallaciousness of this hypothesis, I need not further revert to the matter 
here. 

It seems to me probable that this undue incidence of the increasing 
cancer mortality in men, may be ascribed to the fact that of late, as the 
^result of urbanization, the conditions of life for men have come to resemble 
more closely those for women than heretofore. It is undeniable that 
urbanization has affected far more profoundly the natural life of men 
altering, modifying, and suppressing their ancestral habits than it has 
the natural life of women. Out of these conditions, which comprise a more 
domesticated mode of life, want of proper exercise, and excess of food, 
I believe the present increased cancer mortality has sprung. 



The Concomitant Decline of Tubercle. 

Cancer is a disease more to be dreaded than tubercle, under the con- 
ditions of existence at present obtaining in modern communities where 
the occidental type of civilization prevails ; for, while tubercle has declined 

1 During the twenty years comprised between the decennia 1851-1860 and 1871-1880, 
the increase for males was at the rate of 2'4 per cent, per annum, and for females 1'8 per 
cent, During the period between 1861-1870 and 1891-1897 the annual average increase 
for males was 3'1 per cent., and for females T9 per cent. " Should equal percentages of 
increase be maintained, they would bring up the cancer mortality rate to 1871 per million, 
for both males and females about the year 1932 ; and thereafter the rate for males would 
exceed that for females " (Tatham). The same disparity is shown if we restrict our 
neld to persons aged thirty-five and upwards ; thus, in 1885, 1 in 21 men, and 1 in 12 
women of this age limit, eventually died of cancer ; whereas, in 1905, the corresponding 
figures were 1 in 12 men, and 1 in 8 women. 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 59 



with great rapidity, cancer has increased at a still faster rate, and these 
inversely related changes are still in active progress. In illustration of 
these remarks, it may be mentioned that during the last half of the 
nineteenth century, the cancer mortality for our country tripled ; while, 
during the same period, the tubercle death-rate declined to the extent 
of nearly one-half. If we extend our survey, so as to embrace the sixty- 
five years from 1838 to 1903, these peculiarities are rendered still more 
evident ; for, during this period, the increase in the cancer mortality was 
more than fivefold viz., from 16 per 100,000 living in 1838, to 87 in 1903 ; 
whereas the phthisis mortality, in the same time, decreased more than 
threefold viz., from 380 in 1838, to 119 in 1903. Moreover, the latest 
ascertained cancer death-rate (88 for 1905) is the highest on record ; 
while that for phthisis (114 in 1905) is the lowest. 

Cancer is now a more fatal disease for women than phthisis, the 
respective death-rates for 1905, being 100 for the former and 94 for the 
latter malady ; l it was in 1903 that cancer first gained this lead. 

Unless some great change in the national habits soon takes place, of 
which there is at present no well-marked indication, cancer will ere long 
claim more victims even than phthisis, as is already the case in many 
localities e.g., Hampstead, Clifton, Bath etc. 

This great decline in the tubercle mortality under modern conditions 
of existence, is one of the most remarkable and unexpected facts that the 
study of vital statistics has revealed ; and, rightly apprehended, it throws 
a striking light on the problem of the increase of cancer. 

This correlated variability in morbid proclivity is met with in every 
community, where the modern type of civilization prevails ; for in those 
parts where apparent exceptions occur, as in some districts of Ireland, 
this type of civilization, with its material prosperity, good food, and good 
sanitation, is conspicuous by its absence, as I have ascertained by per- 
sonal investigation on the spot, with regard to Kerry and the " Wild 
West " of Ireland. 

In point of time, these two movements have been coeval, as is shown 
by the following table, indicating the respective death-rates per million 
living, during the latter half of the nineteenth century : 





1851-1860. 


1861-1870. 


1871-1880. 


1881-1890. 


1891-1900. 


Cancer 


317 


384 


468 


589 


754 


Phthisis 


2676 


2475 


2116 


1724 


1391 


Other tuberculous diseases 


807 


765 


,47 


696 


619 



This table shows that, for the country as a whole, the incidence of 
cancer and tubercle vary inversely. 

It is a curious fact, that in many other of the inter-relations of these 
two diseases, an inverse relationship is also noticeable, as I shall have 
occasion to indicate in the sequel. 

In this country a comparatively high and increasing cancer mortality 

1 The cancer death-rates, for 1905, are 75'6 for males and 100'5 for females ; the corre- 
sponding phthisis rates being, for males, 134" 7 and, for females, 94'7. 



60 



THE NATURAL HISTORY OF CAXCER 



implies, according to its extent, a comparatively low and decreasing 
tubercle mortality, and vice versa. 

A similar connexity is noticeable, even where we confine our attention 
only to certain limited areas, as Haviland * has very clearly demonstrated. 
He worked out the death-rates for each of these diseases, for every one 
of the 630 registration districts, with such corrections for age and sex 
distribution as the available data permitted. He proceeded to indicate 
on each of two identical maps, the varying death-rates from each malady, 
by colouring the different areas blue for those above the average, and 
red for those below, with intermediate tints for the corresponding degrees 
of mortality. Having completed this laborious task, he found, on com- 
paring the two maps, that just such inter-relations as those above men- 
tioned, prevailed in almost every district. 

Some years ago, William Farr 2 selected thirteen registration districts, 
widely separated from one another, as examples of the favourable influence 
of improved sanitation, good drainage, and good water-supply on the 
public health. During the three decennia over which this inquiry 
extended, all the selected districts showed progressive declines in the 
general death-rate, as well as in the tubercle mortality ; yet, in spite of 
these gains, the cancer death-rates were shown to have markedly in- 
creased, in every one of these thirteen districts. 

Within the limits of individual large towns, as I shall presently have 
occasion to prove, a similar state of affairs is almost everywhere notice- 
able. Where the population is densest, there the tubercle mortality is 
highest ; and it is just in these densely populated areas that the cancer 
mortality is lowest. 

The increase of cancer and the decrease of phthisis in London during 
the latter half of the nineteenth century, are shown by the following 
data 3 



1851 to 1860 
1861 1870 
1871 1880 
1881 1890 
1891 1900 



Cancer Death-rate Phthisis 

per 100,000 Living. Death-rate. 



286 
284 
251 
209 
183 



For subsequent years the figures are : 



1901 
1902 
1903 
1904 
1905 



.. 96 

.. 92 

. 93 



171 
160 
155 
162 
142 



The Report of the Medical Officer of Health for 1903, shows that well- 
to-do, salubrious Hampstead has the highest cancer death-rate of any 
Metropolitan borough viz., 120 per 100,000 living* while its death- 

" Geographical Distribution of Disease in Great Britain," 2nd edit., 1892 ; 
earlier work, Geography of Heart Disease, Cancer, and Phthisis," 1875 
Registrar-General's Thirty-seventh Annual Report. 
Report of the Medical Officer of Health of the County of London for 1903. 
Corrected for age and sex distribution, for hospitals, etc. 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 61 



rate from phthisis is the lowest viz., 73. Next to Hampstead, the 
wealthy communities of Marylebone (comprising some of the best resi- 
dential quarters of the West End), and Chelsea suffer most from cancer, 
their respective death-rates from this cause being 119 and 106 ; while 
their mortality from phthisis is decidedly below the average (155) viz., 
151 and 149 respectively. 

Of the six metropolitan boroughs having the highest phthisis mor- 
tality viz., Holborn, Shoreditch, Southwark, Finsbury, Bethnal Green, 
and Stepney only one, Southwark, has a cancer death-rate above 
average (96), its figure being 104, and this is an exceptional occurrence. 

Wands worth, with a cancer death-rate of 102, has the low phthisis 
death-rate of 96. 

As another example of this connexity, the case of Bristol may be 
instanced, with its well-to-do and salubrious suburb Clifton, and its busy 
working-class and comparatively poor district of St. Philip, for which the 
respective mortality data in 1903, were as follows : 





Bristol. 


Clifton. 


St. Philip. 


Total population 
Total deaths 
General death-rate 


338,895 
4822 
142 
281 


44,435 
494 
111 
46 


48,986 
711 
145 
38 


Cancer death-rate 
Phthisis deaths 
Phthisis death-rate . . . . .' 


83 
366 
103 


103 
29 
65 


77 
55 
110 



In nearly all modern communities where statistical data are pub- 
lished, similar relations prevail between these two diseases, of which I 
shall subsequently have occasion to cite many instances. Thus, Hungary, 
with the lowest cancer death-rate of any country in Europe (33), has the 
highest tubercle mortality (387). International vital statistics are, how- 
ever, at present in too backward a condition to enable us to make a 
really satisfactory study of these inter-relations in every community. 
Thus, for France, Denmark, and Sweden, the available data refer only to 
the town population, which in these communities comprises only a small 
part of the total population ; then, as to Switzerland, there are no official 
data for the whole country. Moreover, several communities are now in 
such a state of acute transition, owing to the sudden swarming to the 
towns etc., as to render their vital statistics for the time being unreliable 
for such comparisons. 

In this connexion it is worth noting that the increase of cancer and 
the decline of tubercle, seem to have set in earlier in Great Britain than 
in other countries. Moreover, the British vital statistics are unusually 
complete and accurate with regard to these matters ; and they have the 
further great advantage of having been compiled on a uniform plan, for 
a long series of years. 

I regard this decline in the prevalence of tuberculous disease, as the 
direct outcome of the better food and improved hygienic conditions, for 
which we are indebted to our increased national prosperity ; and I shall 
endeavour to show that conditions of this kind, by their action in another 



62 THE NATURAL HISTORY OF CANCER 

direction, are also mainly responsible for the augmented cancer mor- 
tality. 

Moreover, it seems to me exceedingly probable, from considerations 
derived mainly from the study of the family history of cancer patients, 
that many of those thus saved from tubercle, eventually perish from 
cancer. Indeed, I think the increase in the latter disease has largely 
been brought about in this way. 

Indigence, insufficiency of food, overcrowding, and bad sanitation, 
which favour the generation of most diseases, especially tuberculous and 
contagious affections, exercise no such power over the incidence of cancer, 
which flourishes most under just the opposite conditions. 

Etiological. 

The precise period at which these remarkable changes in the morbid 
proclivities of the population commenced, probably dates back tp the 
latter part of the eighteenth century ; at any rate, they were certainly 
in operation during the whole of the nineteenth century. 

It is in the spread of industrialism that their origin will be found, 
and especially in that particular phase of it, characterized by the utiliza- 
tion of steam as a motive power. 

This kind of progress has entailed two remarkable effects : (1) urbaniza- 
tion, the most stupendous environmental change that the human race has 
ever experienced ; and (2) enormous increase of riches with widespread 
material prosperity. 

It now remains for me to show how, by the interaction of these 
factors, cancer has increased, while tubercle and other maladies have 
markedly diminished. 

1. It is generally agreed that the stability of the equilibration of the 
y^ constituent elements of living bodies, is more profoundly affected by 
sudden and violent changes in the environment, than by any other group 
of circumstances. The invariable tendency of such changes is to render 
the organisms that survive them more plastic that is to say, more prone 
to deviate from the normal routine of their growth and development. 
The natural history of cancer shows that it is a disease belonging to this 
category. Any sudden, far-reaching, environmental change of some 
duration is probably potent in this direction, as may be inferred from 
the undue proclivity to cancer of immigrants into the United States, 
Australia, New Zealand, etc., to which I have previously called atten- 
tion ; and there are good reasons for believing, as I shall subsequently 
have occasion to indicate, that the sudden change from poverty and 
want, to riches and plenty may, per se, be equally potent e.g., Switzer- 
land, Denmark etc. 

The nineteenth century has been variously called the age of steam, 
the age of iron, the age of factories and industrialism, the age of natural 
science, the age of the microscope and of the microbe, according to the 
standpoint of the individual observers ; but, for the great majority of the 
Western world, the past century will for ever be memorable as the age of 
urbanization. This tremendous vicissitude, suddenly precipitated, un- 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 63 

doubtedly constitutes the most profound and far-reaching environmental 
change, that the human race has ever experienced ; and in England, where 
80 per cent, of the population are now town-dwellers, it has gone further 
than in any other community. The last century has witnessed the 
transition of millions of people from rural life and surroundings, to life 
in large towns, where all the conditions of existence are so different. I 
believe that the increase of cancer in this country, has sprung out of 
impulses thus determined. 

Until the advent of the nineteenth century an open-air existence had, 
from time immemorial, been the lot of the great majority of EngUsh 
people, who depended for subsistence mainly upon agricultural pursuits. 
Since that time this old-established mode of life has been radically and 
rapidly changed. 

The first official enumeration of the population was made in 1801, 
when, of the 9,000,000 of people, more than three-fourths lived in the 
country. A century later, in 1901, the population had increased to over 
32.500,000, of whom less than one-fourth now lived in the country. 

In 1801, there were in England and Wales sixty-one towns, with a 
population of 2,163,698 inhabitants ; in 1851, these towns had increased 
to 580, and their population to 6,254,251, or 35 per cent, of the entire 
population. Twenty years later, in 1871, the towns numbered 938, and 
their population was 14,000,000, or 61 per cent, of the entire population ; 
in 1881, over 70 per cent, of the population was urban ; in 1891 this 
proportion had increased to nearly 72 per cent. ; and, in 1901, the town 
dwellers comprised 77 per cent, of the entire population. The urbaniza- 
tion of the English people is now wellnigh complete, for most of the 
present so-called rural population are suburbanites, or immigrants from 
the towns. Moreover, the towns have now become the chief breeding- 
grounds for the replenishment of the race, the rural population having 
lost its former productiveness in this respect. 

Thus, in the course of a comparatively brief span, the conditions of 
existence for the whole nation have undergone more profound changes, 
than hundreds of centuries had previously wrought. 

2. One of the most potent and widespread effects of the conditions of 
life incidental to urbanization, on the health of those involved in its influ- 
ence, is its tendency to induce degenerative changes which impair the 
capacity of those affected to resist various morbid excitations. It will 
probably be found that these changes ultimately depend upon perverted 
cellular metabolism, which is, I believe, the common root whence spring 
such diverse morbid manifestations as tubercle, cancer, and insanity. 

Tubercle is a malady naturally tending to increase with increasing 
density of population, and especially with urbanization. If, therefore, 
this malady has not only been arrested, but has immensely declined, in 
spite of the rapid spread of urbanization, there must be some good 
reason for it. 

This reason is sufficiently obvious. It is the unexampled increase in 
material prosperity, which the new conditions of existence have brought 
with them. Prosperity has given our people good food and good sanita- 
tion ; and thus the evil tendencies of urbanization have, to a certain 



64 THE NATURAL HISTORY OF CANCER 

extent, been mitigated. Many of those who have acquired morbid pre- 
dispositions owing to urbanization, now escape the fate that would have 
overtaken them under other conditions. It would, however, be a mis- 
take on this account to regard such persons as being normally constituted. 
Their degeneracy is none the less real because it is not obviously manifest. 
According to my belief, it is from such persons and their descendants, 
that the ranks of the great cancer army are being constantly recruited. 
This view of the question throws an interesting sidelight on the curious 
.' paradox, in which there certainly is much truth, that a high cancer 
mortality is an indication of general prosperity and good sanitary con- 
ditions. 

Probably no single factor is more potent in determining the outbreak 
of cancer in the predisposed, than excessive feeding. There can be no 
doubt that the greed for food manifested by the people of modern com- 
munities, is altogether out of proportion to the requirements of their 
present mode of life. Many indications point to the gluttonous con- 
sumption of proteids especially meat which is such a characteristic 
feature of the age, as likely to be specially harmful in this respect. Statis- 
tics show that the consumption of meat has for many years been 
increasing by leaps and bounds ; * and it has now reached the amazing 
total of 130 pounds per head per year (men, women, and children), which 
is nearly double what it was half a century ago, when the conditions of 
life were less incompatible with high feeding. Among the well-to-do 
classes, the meat consumption has been estimated to amount to from 
180 to 330 pounds per head per year. In addition to these totals, large 
quantities of game, poultry, rabbits, etc., must be included, as well as a 
fish consumption of 75 pounds per head per year, 12 pounds of cheese, 
14 gallons of milk, and 80 eggs each a year. 

When excessive quantities of such highly stimulating forms of nutri- 
ment are ingested by persons whose cellular metabolism is perverted, it 
seems probable that there may thus be excited, in those parts of the body 
where vital processes are still capable of rejuvenescence, such excessive 
and disorderly cellular proliferation as may eventuate in cancer. No 
doubt other factors co-operate besides those I have already mentioned, 
and among these I should be inclined to name deficient exercise, and 
probably also lack of sufficient fresh vegetable food. 

Such influences as are comprised under the terms alimentation and 
domestication, seem to me to be of paramount importance in the aetiology 
of cancer. 

With regard to the influence of diet rich in proteids on the incidence 
of tubercle, I think there can be no doubt that its effect is just the con- 
verse of that which we have seen in the case of cancer. That is to say, 
when the proportion of proteids, especially meat, in the dietary is too 
small, tubercle is very apt to supervene, even when climatic and hygienic 
conditions are favourable ; and, besides the proteids of meat, the fats 
also seem to have anti-tuberculous properties. 

1 Report of Committee of Royal Statistical Society of Great Britain, December, 
IUU4 ; tor other data see also Mulhall's great work, " The Industries and Wealth of 
Nations," 1896. 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 65 

As an example of this, the case of Ireland may be cited, where, as 
indicated in the preceding chapter, conditions of existence which are 
predominantly rural, are associated with poverty and a diet unduly 
deficient in proteids. 1 Under these circumstances, the cancer mortality 
is much lower than in England, while that from tubercle and phthisis is 
much higher ; and this in spite of the more favourable climatic conditions 
and rural surroundings. Moreover, it is significant that in the " Wild 
West " e.g., in Kerry, where these conditions are most en evidence, and 
the people are notoriously underfed the cancer mortality is the lowest 
in the United Kingdom, while the tubercle mortality is exceedingly 
high. 

Per contra, in the one part of Ireland where industrialism and its 
concomitants have made marked progress, and where material prosperity 
is most noticeable e.g., in Ulster the cancer death-rate is the highest, 
while that from phthisis is comparatively low. 

In fact, the increased cancer mortality in Ireland during recent years, 
is mainly due to the augmentation of the malady among the industrial 
population of Ulster, Dublin etc. 

It now remains for me to indicate briefly some of the salient features 
as to the extraordinary prosperity, with which this increase of cancer has 
coincided. It is all the more necessary for me to do this, because some 
pathologists still entertain and teach very erroneous views on this sub- 
ject. These have received their apotheosis from Sir W. J. Sinclair, 2 who 
says : " If we could place all the lower orders who suffer from privation 
and depressing environment, for a generation or two in the position of 
the more favoured, we should stamp out cancer." 

As all the information at my disposal is totally opposed to any such 
conclusion, it seems desirable to briefly review this evidence. 

During the last half-century the wealth of the community has more 
than doubled, and is now estimated to amount to 15,000 millions sterling, 
the annual income being 1,750 millions. The present annual expenditure 
is estimated at 1,386 millions, of which 468 millions, or 34 per cent., is 
spent on food and drink (Giffen) ; and in the case of the working classes, 
50 per cent, of their earnings are thus spent. During this period the 
income-tax assessments have increased from 300 millions to 833 millions 
sterling. This country is still the wealthiest in the world, although its 
wealth is proportionally less widely diffused among the people than is 
the case in many other countries. That the great mass of our people 
have, however, largely participated is evidenced by the fact that the 
accumulated savings of the working classes now total 531 millions sterling ; 
and by such other considerations as I will now proceed to mention. 

Pauperism has diminished by more than one-half viz., from 5-3 per 
cent, of the total population in 1851 to 2-4 in 1901 and it is now less 
than at any previous period of our history. Crime, likewise, has steadily 
declined. 

Wages have gone up as much as from 25 to 50 per cent. ; while, at 

1 In 1895 the meat consumption of Ireland was estimated by Mulhall at only 40 pounds 
per head per year, or barely a third of the amount consumed in England. 

2 Allbutt's " System of Gynaecology," 1897, p. 657. 

5 



66 THE NATURAL HISTORY OF CANCER 

the same time, the prices of aU the really essential commodities of life 
have fallen to an extraordinary extent. 1 

In the same time the consumption of meat per head has more than 

U The general death-rate declined from 22-7 in 1851-1855, to 18-2 in 
1900, to 15-2 in 1903 ; and the population has steadily increased. 

The mortality from zymotic, tuberculous, and many other diseases, 
has markedly diminished, and sanitary conditions have greatly improved. 
In short, the bulk of the people are better paid, better housed, and better 
fed than ever they have been before that is to say, just such conditions 
have prevailed as Sinclair alleges are necessary to stamp out cancer yet, 
instead of having decreased during this period, the cancer mortality has 
tripled. 

In further support of my contention, I would point out that the 
Registrar-General's Reports show that the cancer mortality is lowest where 
the conditions of life are hardest, the surroundings the most squalid, the 
density of population greatest, the tubercle mortality highest, the general 
and infantile mortality highest, and where sanitation is least perfect in 
short, among the poor of the industrial classes in our great towns ; 
whereas, among the wealthy and w r ell-to-do, where the standard of 
health is at its best, and life is easiest, and where all the conditions 
of existence are just the converse of the foregoing, there the cancer 
mortality is highest, as I shall subsequently have occasion to show more 
in detail. 

As an indication in the same direction, the experience of those engaged 
in prisons, workhouses, and lunatic asylums may be cited ; which is to 
the effect that cancer is comparatively rare among the inmates of such 
institutions, as it is also among the intemperate. Of like import is the 
fact that cancer is so fearfully common in civilized communities ; whereas, 
among savages, it is almost unknown. Moreover, in the animal w r orld, 
it is among the domesticated varieties that malignant and other tumours 
are usually met with : in a state of nature such diseases are almost 
unknown. 

That cancer is a disease of persons whose previous life has been 
healthy, and whose nutritive vigour seems to promise long life, is a 
statement in which I entirely concur. Long-continued observation of 
cancer patients, in the early stage of the disease, has convinced me that 
most of those affected are large, well-nourished persons, who appear to 
be overflowing with vitality. Such types are indicative of hypernutri- 
tion. The small, pale, ill-nourished, and overworked women, of the type 
so familiar in Lancashire and other industrial centres, are seldom afflicted 
with this disease. 

The natural functions of female cancer patients are performed with 
ease and regularity. Their sexual health is vigorous, the capacity for 
reproduction beginning earlier and lasting longer than in the generality 

1 The Report of the Royal Commission on Agriculture (1897) shows: "That 
during the last quarter of a century there has been a fall of over 40 per cent, in the price 
of staple cereals, which in the case of wheat is 50 per cent. ; that in beef the fall has been 
from 24 to 40 per cent., and in mutton from 20 to 30 per cent. ; in dairy produce the price 
declined 30 per cent. ; in potatoes 20 to 30 per cent.," etc. 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 67 

of women. Just so is it with regard to marriage, for a greater propor- 
tion of these cancer patients marry than of the female population in 
general. Moreover, they marry earlier, and commence to have children 
sooner, than the generality of married women ; and their fertility is much 
above the average. All these things indicate a certain vital exuberance, 
which is characteristic. 

The great majority of such persons whose life-history I have investi- 
gated, have been well fed and well housed, having had nothing to do 
but to look after their own domestic establishments. They have usually 
enjoyed excellent health, most of them having had no serious illness 
since youth, rheumatic fever and rheumatism being the commonest 
diseases from which they have suffered. 

In short, the ensemble of facts relative to the life-history of cancer 
patients shows, that they have almost invariably led regular, sober, and 
industrious lives. Persons of drunken and dissolute habits are com- 
paratively seldom affected. In the course of my investigations into the 
life-history of female cancer patients, I have been much struck by the 
extreme rarity with which signs of syphilis etc. are met with in such 
persons. 

Thus, of 325 female cancer patients consecutively under my observa- 
tion, not a single one had ever been addicted to prostitution, so far as I 
could ascertain ; and, what is still more remarkable, only a single one 
presented undoubted signs of having had syphilis. 

The marked fecundity of these cancer patients, and the rarity of 
sterility and abortion among them, all point in the same direction ; for 
sterility and abortion are of frequent occurrence in prostitutes and the 
syphilitic. 

Considerations of this kind negative the doctrine of cancer being 
morbus miserice. They point to the greater prevalency of the disease 
among the well-to-do and easy-going, who habitually eat more than is 
good for them. Such influences as are comprised under the terms 
" alimentation " and " domestication," seem to me to be of paramount 
importance in the aetiology of cancer. 



Scotland. 

For the last half-century the Scotch and English cancer death-rates 
have been singularly alike ; and they have increased pari passu, the Scotch 
figures generally being slightly in excess of their English counterparts as 
follows : 



1861 to 1870 

1871 1880 

1881 1890 

1891 1900 

1900 

1901 

1902 

1903 

1904 

1905 



Cancer Death-rate 
per Million Living. 

.. 416 

.. 486 

.. 578 

.. 739 

.. 800 

.. 820 

.. 830 

.. 840 
. 850 



52 



68 



THE NATURAL HISTORY OF CANCER 



In Scotland, as in England, the increase of the disease has affected 
both sexes, the corresponding death-rates of each sex in the two countries, 
being very much alike ; but the disproportionate increase among males, 
is less marked in the Scotch than in the English returns. The Scotch 
figures are as follows : 



L .. 



1881 
1885 
1890 
1895 
1900 






1 


lale Cancer ] 
Death-rate. 

390 .. 
420 .. 
470 .. 
560 .. 
640 .. 


"emale Cancer 
Death-rate. 

630 
690 
740 

880 
950 


1901 
1902 
1903 
1904 
1905 




. 




670 .. 
660 .. 
690 .. 
680 .. 
700 .. 


970 
990 
970 
1020 
1070 



The increase of cancer in Scotland, has been accompanied by the same 
concomitants as in England that is to say, by diminution of the mor- 
tality from tubercle and zymotics, decline of the general death-rate, 
progressive population, and other signs of material prosperity ; while, at 
the same time, insanity, suicide, etc., have increased. 

Thus, the tubercle death-rate declined from 3,600 per million living 
in 1864, to 2,300 in 1900, and to 2,070 in 1905. In like manner, the 
death-rate from phthisis, which was 2,220 in 1883, fell to 1,660 in 1900, 
and to 1,460 in 1903, and these declines have affected both sexes. 

As in England, these concomitants have coincided with urbanization, 
and great increase of material prosperity. 

With regard to the former, in 1801, 16-8 per cent, of the Scotch popula- 
tion was urban ; in 1851 this percentage had increased to 26-9 ; and in 
1902 to 75-3. The environmental change has, therefore, been almost as 
complete and abrupt as in England. 

With regard to the latter, the proportionate increase in wealth and 
wages has been nearly as great in Scotland as in England ; and it has 
likewise been accompanied by abundance of food and improved sanita- 
tion, whereby the depressing and disease-producing tendencies of urban- 
ization have been combated. 

As evidence of this, the decline of pauperism may be instanced viz., 
from 4-1 per cent, in 1869 to 2-3 per cent, in 1903. 

During the last half-century the wealth of Scotland has enormously 
increased ; and, next to England, Scotland now is one of the wealthiest 
countries in the world, the average wealth per inhabitant having been 
estimated at 260 by Mulhall in 1896, as against 330 for England. 

With this change, the dietary habits of the people have also been 
radically altered. Porridge is no longer the staple food as formerly ; 
meat has now taken its place, especially in the towns. Thus, the meat 
consumption of Scotland in 1895, has been estimated at 180,000 tons per 
annum ; whereas that of Ireland only amounted to 80,000 tons, although 
its population then exceeded that of Scotland. 

It accords with the foregoing, that cancer is found to be least prevalent 
in the islands of Scotland (56 per 100,000 living in 1900), where the 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 69 

people are poor and the diet is mainly vegetarian ; and it is just in these 
localities, notwithstanding the rural conditions of existence, that phthisis 
is most prevalent (182 per 100,000 living in 1900). 

Similar conditions prevail in the Shetland Islands. 

With regard to the capital, the cancer death-rate of Edinburgh main- 
tains a higher average than that for any other town ; and the rate has 
increased from 81 per 100,000 living in 1881, to 97 in 1891, to 109 in 1901, 
and to 135 in 1905 ; while, at the same time, the tubercle mortality has 
declined, the death-rate for phthisis now being very low. 

In the principal towns similar changes have taken place. Thus, while 
the cancer death-rate for these increased from 70 per 100,000 living in 
1891, to 86 in 1902; the phthisis death-rate declined from 218 in the 
former period, to 161 in the latter. 

Among the large towns, Glasgow, where the stress of life is con- 
siderable, has long been remarkable for its comparatively low average 
cancer mortality, coeval with a high death-rate from phthisis ; but with 
the improving conditions of existence for the masses in comparatively 
recent times, the cancer mortality has steadily increased, while that 
from phthisis has decreased. Thus, the cancer death-rate has augmented 
from 60 per 100,000 living in 1891, to 85 in 1902 ; and the phthisis mor- 
tality has decreased from 243 the former year, to 177 in the latter. 

In like manner, the county of Berwick, with the highest cancer death- 
rate in Scotland, has an exceptionally low phthisis mortality. 

Thus, in Scotland, as in England, it is evident that the increasing 
incidence of cancer goes hand-in-hand with diminishing incidence of 
tuberculous and zymotic maladies, with decline of the general mortality, 
progressive population, and increased material prosperity, of which the 
determining factors are to be found in those great changes wrought in 
the habits and mode of life of the people, by industrialism and urbaniza- 
tion, as I have previously indicated. 



Ireland. 

The vital statistics of Ireland during the last sixty years, have been 
so perturbed by the constant diminution of population, owing to emigra- 
tion en masse, with the consequent reduction in numbers by nearly one- 
half ; that, in their crude state, they are only available in a certain general 
way, for comparison with the corresponding English and Scotch data, 
derived from progressive populations, which have nearly doubled their 
numbers in the same period. In consequence of this disturbing factor, 
the Irish population contains fewer children and young adults, but more 
elderly persons, especially females, than either the English or Scotch 
populations, and its average age is much higher. The resultant effect of 
these perturbing influences, has been to exaggerate the ostensible cancer 
death-rate of Ireland, as compared with that of England and Scotland. 
Even so, however, the crude cancer death-rate of Ireland, is much less 
than that of either of the sister communities ; and during the last half- 
century, its comparative rate of increase has also been rather less. Thus, 



70 THE NATURAL HISTORY OF CANCER 

the Irish cancer death-rate increased from 27 per 100,000 living in 1864 
(when registration first came into force), to 61 in 1900, to 65 in 1901, to 
67 in 1903, and to 79-3 in 1906, the figures for intervening years being 33 
in 1870, 34 in 1880, 39 in 1885, 46 ir. 1890, and 50 in 1895. 

The highest cancer death-rate is found in well-to-do, prosperous 
Armagh (104) ; and the lowest in poverty-stricken Kerry (26). 

In Ireland, as in England, more women die from cancer than men, 
the numbers for 1906 being 1,566 males and 1,915 females. The increase 
of the disease has likewise affected both sexes, but with undue incidence 
on males. 

Pauperism and insanity are more prevalent in Ireland, than in any 
other division of the United Kingdom ; and they are both on the increase. 

The prevalence of tubercle in Ireland, moreover, shows no such ten- 
dency to diminution as in England. Indeed, the mortality from this 
cause slightly increased during the latter part of the nineteenth century 
viz., from 260 per 100,000 bring in 1871-1880, to 290 in 1897-1900 ; and 
it is the same with regard to phthisis, the death-rate having increased 
from 192 in 1871, to 203 in 1906, after having been stationary for several 
years. 

Although Ireland is a very much poorer country than England, and 
although its material prosperity has, during the last half-century, aug- 
mented much more slowly than that of England ; yet, as Dr. Grimshaw 
has shown, 1 its aggregate wealth has steadily increased, notwithstanding 
the decrease of population and the poverty of the bulk of the people. 
This result is mainly due to the growth of manufacturing and industrial 
enterprises in a few localities e.g., in Ulster, in Dublin and its vicinity, 
and in Carlow, for which the community is mainly indebted to persons 
of Anglo-Scotch descent, who are numerous in these localities. Now, it 
is just in these places that the highest cancer death-rates are found. For 
instance, Ulster, the seat of the great linen and other industries, had a 
cancer death-rate of 77 in 1901, which is much above the average ; while 
its phthisis death-rate was 210. 

Moreover, it is mainly owing to augmentation of the disease in these 
localities, that the increased cancer mortality of Ireland, as a whole, is due. 

In almost all other parts of Ireland, where rural conditions of exist- 
ence prevail, and the bulk of the people are decidedly poor and ill-fed, 
as compared with their English compatriots, cancer is comparatively 
rare, while tubercle is very prevalent. 

Switzerland. 

There are no official statistics relating to the causes of death for the 
whole country ; but, according to Nencki's research, 2 which is based on 
the cantonal reports, cancer is more prevalent in Switzerland than in 
any other country, the death-rate from this cause having augmented 
from 114 in 1889, to 132 per 100,000 living in 1898. This high cancer 

2 e P rt of tne Commission on the Financial Relations of England and Ireland, 1894. 
" Die Frequenz und Verteilung des Krebses in der Schweiz," etc Zits f schw 
Statistik, 1900, vol. ii., p. 332. 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 71 

mortality is associated with the comparatively low phthisis death-rate 
of 189. 

During the same period tubercle has steadily declined, the phthisis 
death-rate having fallen from 234 in 1876-1880, to 187 in 1901. 

Three-fourths of Switzerland is mountainous, comprising large areas 
of forests. The proportion of town-dwellers is a quarter, and it is in- 
creasing. Of its 1,500,000 workers, two-thirds are engaged in industrial 
and commercial occupations, and only one-third in agriculture. 

About two-thirds of the people are of German descent, the remainder 
being of French and Italian origin. 

Half a century ago, Switzerland was an exceedingly poor country ; 
now it is one of the most prosperous and well-to-do communities in 
Europe, the average wealth per inhabitant being 165, or 8 more than 
in Germany (Mulhall). 

There are no millionaires in Switzerland, and no paupers ; so that 
prosperity is even more widely diffused than in France. 

The population has been steadily progressive, with a diminishing 
general death-rate ; and the meat consumption is considerable (85 pounds 
per head per year in 1895). 

The cancer mortality varies greatly in the different cantons viz., 
from 204 per 100,000 living in wealthy Lucerne, to 36 in poverty-stricken 
Valais. 

Denmark. 

Next to Switzerland, Denmark is reputed to have the highest cancer 
death-rate of any country in Europe viz., 130 per 100,000 living in 1900 ; 
but statistical data are available only for the towns, the inhabitants of 
which comprise but a quarter of the entire population ; so that the figure 
for the whole country, although high, w r ould be considerably less than 
the above. 

In these same towns, with this high cancer mortality, we find asso- 
ciated the very low phthisis death-rate of 150. 

In 1886-1887 the cancer death-rate of the Danish towns was 109, so 
that considerable increase has since taken place. During the same period 
the incidence of phthisis has markedly declined viz., from about 300- 
in 1870-1874, to 150 in 1900. 

Denmark is an agricultural country whose population, notwith- 
standing the absence of any great development of manufacturing in- 
dustries, has nevertheless in a comparatively brief period, experienced a 
sudden change from serfdom and poverty, to freedom and great pros- 
perity. Serfdom was only abolished at the end of the eighteenth cen- 
tury ; and since then these emancipated serfs have largely become yeomen 
proprietors of their small holdings; so that, in 1890, 71,000 peasant 
proprietors owned four-fifths of the total soil. Their present state of 
prosperity is well indicated by the fact that : "the ratio of wealth per 
head of the population is now higher than in any other country of Con- 
tinental Europe, except France " (Mulhall). 

The only large city in Denmark is Copenhagen, w T hose inhabitants 
total one-sixth of the entire population. 



72 THE NATURAL HISTORY OP CANCER 

The cultivated area is proportionally larger than that of other European 
countries, and there are but few forests. 

Denmark produces hardly any coal or minerals, so that manufacturing 
industries are much less dominant than in most modern communities. 

France. 

In dealing with French vital statistics, due allowance must be made 
for the fact that they relate only to the towns, which comprise a popula- 
tion of about 12,000,000 out of a total of nearly 39,000,000. 

These data show that cancer 1 is very prevalent, and that the incidence 
of the malady is increasing. 

For Paris, the following figures 2 indicate the cancer death-rates : 
1865, 84 ; 1870, 91 ; 1880, 94 ; 1890, 108 ; and 1900, 120. 

For all towns of above 10,000 inhabitants (omitting Paris), the figures 
are : 1887, 76 ; 1890, 91 ; 1895, 100 ; and 1900, 106. 

The lowest cancer death-rates are found along the Mediterranean 
littoral (Corsica, 32 etc.) and in Brittany (Finisterre, 38), where the 
people are comparatively poor ; and the highest are in prosperous Nor- 
mandy and the adjacent departments (Rouen, 173 ; Eure-et-Loire, 167 
etc.). 

The French population, although still predominantly rural, has under- 
gone much urbanization, the ratio of urban to rural inhabitants having 
increased from 24 in 1846 to 43 in 1900; and this change is almost entirely 
due to the disproportionate growth of the large towns e.g., Paris, Lyons, 
Marseilles, Lille, Bordeaux etc. 

The tubercle mortality of the towns is high ; and although Paris (439 
in 1887, to 394 in 1901), and some of the largest cities, show improvement 
in this respect, in other towns the decline is but slight. The phthisis 
mortality for all the towns, which was 245 in 1877, had declined to 213 
in 1903. 

Next to England, France is the richest country in Europe, and its 
wealth has been steadily increasing throughout the last century ; but 
the wealth of France is much more widely diffused than that of England. 
Thus, while the working classes in the two countries number about the 
same, the French workers own 4,330 millions worth of property, against 
only 566 for their English compeers. The riches of France are, as it 
were, clotted in the large towns ; and these, as I have previously indicated, 
everywhere have a higher cancer mortality than the small towns, chefs- 
lieux d'arrondissement etc. 

Sweden. 

As in other Scandinavian countries, the cancer mortality of Sweden 
is high. Statistics exist only for the towns, of which but two (Stock- 
holm and Gottenburg) contain more than 100,000 inhabitants. The 
urban population comprises about one-fifth of the total inhabitants. 
" Cancer et autres tumeurs." 

2 For these data I am indebted to Dr. J. Bertillon ; see also his annual publications 
in the " Annuaire Statistique de la ville de Paris," and for the other towns the " Annuaire 
Statistique Sanitaire des villes de France," etc. 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 73 

Judged by death-rates, the Swedes are one of the healthiest races in 
the world, for their general death-rate during the last decade was only 
16-4, the corresponding figures for Norway and England, the next best 
on the list, being 16-9 and 18-8 respectively. 

According to Quensel, there was progressive increase in the mortality 
from cancer during the last quarter of the nineteenth century viz., from 
80 per 100,000 inhabitants in 1875-1879, to 97 in 1895-1899. In the 
former period the deaths from cancer amounted to 3-37 of the total 
mortality ; in the latter to 6-27. In 1900, the cancer death-rate had 
increased to 102. To this increase men have contributed more than 
women, the sex ratios, which in 1875-1879 were 100 males to 192 females, 
having changed to 100 to 150 in 1895-1899. 

Tubercle is very much less prevalent in Sweden than in most European 
countries, and the mortality from this cause has declined. Thus, the 
phthisis death-rate for the towns, which was 280 in 1886-1887, in 1900 
had fallen to 170. 

A curious feature revealed by Quensel's research is, that the cancer 
death-rate of the small towns exceeded that of the large ones. Thus, 
the rate for communities of less than 2,000 inhabitants was 100 ; for 
those of from 2,000 to 10,000, 90 ; and for those of over 10,000 inhabi- 
tants, 85. 

As previously mentioned, this anomaly, taken with other similar 
indications, seems to show that the incidence of cancer is determined 
more by local conditions of existence, than it is by urban or rural life 
per se. 

The average consumption of flesh food per head per year is only 
67 pounds (Mulhall) ; but the Scandinavians rely for their proteids quite 
as much on milk, cheese, and fish, of which immense quantities are con- 
sumed, as they do on meat. From what I have myself seen of the dietetic 
habits of the Scandinavians, I have come to the conclusion that their 
consumption of proteids exceeds that of most European nations. 

Norway. 

In Norway, the population is even more predominantly rural than in 
Sweden ; and, besides agriculture, the lumber trade, fishing, commerce, 
and cattle-rearing, are their chief resources. 

The Norwegian statistics, unlike those of Sweden, apply to the whole 
population ; and they show steady increase in the cancer mortality. Thus, 
in 1880, the rate was 43 ; in 1890, 61 ; and in 1900, 92. The tubercle 
mortality is almost as low as that of Sweden. The highest cancer mor- 
tality is met with in the centres of the fishing, shipping, and timber 
industries, where the people are financially the most prosperous. 

Holland. 

This country, which consists of a fertile alluvial plain traversed by 
rivers and canals, is noted for its prosperity, which is largely due to 
agriculture. The cancer mortality is high and increasing. In 1867-1879 



74 THE NATURAL HISTORY OF CANCER 

the cancer death-rate was 49 ; in 1884-1888, 66 ; in 1890, 79 ; in 1900, 93 ; 
in 1903, 99 ; and in 1905, 101. Its tubercle mortality is decidedly low 
viz., about 180 while in 1903 the death-rate from phthisis was only 132, 
and both are declining. 

The lowest cancer death-rate (77) is in the comparatively poor and 
unproductive province' of Drenthe, where large pauper colonies have been 
established. 

In Amsterdam, the cancer mortality increased from 38 in 1891, to 
78 in 1900 ; while the death-rate from phthisis fell from 260 in 1862-1863, 
to 177 in 1897-1901. 

Germany. 

According to Maeder * and Wutzdorff, 2 whose researches are based 
upon official data, 3 cancer has of late increased in Germany, while tubercle 
has declined ; and these changes have coincided with increased general 
prosperity. 

The cancer death-rate, which was 59 in 1872, increased to 71 in 
1900. Per contra, the tubercle mortality has declined 38 per cent, since 
1875. 

In Berlin, the cancer rate increased from 57 in 1870-1882, to 109 in 
1899 ; while phthisis declined from 310 in 1876, to 190 in 1901. 

The Hamburg cancer rate increased from 71 in 1872, to 97 in 1898. 
During the same period, the mortality from phthisis declined from 340 
in the former year to 194, in the latter ; and there was also marked dimi- 
nution in the general death-rate. 

Of the constituent States of Germany, the rich southern ones have 
much the highest cancer death-rates. 

Baden heads the list (101), and, as Maeder has shown, the disease has 
increased there. 

Bavaria comes next, with an increase from 56 in 1880, to 98 in 1900. 
In Munich the increase was from 88 in 1890, to 119 in 1900. 

In Saxony, the increase has been from 69 in 1876-1885, to 95 in 1900. 
During about the same period phthisis declined from 231 (1873-1875), 
to 190. Of late, the high Dresden cancer rate has been about stationary 
viz., 123 in 1891, and 125 in 1900. 

In Stuttgart, the cancer death-rate increased from 76 in 1891, to 127 
in 1900. 

The average cancer mortality in Prussia is much less than that of 
these southern States, but even here the disease has increased viz., 
from 31 in 1881, to 59 in 1900, and to 60 in 1905. The phthisis death- 
rate has declined from 360 in 1851, to 150 in 1901 ; but insanity has 
notably increased. 

Cancer is probably more prevalent in Schleswig-Holstein (76), where 
Danish conditions of existence prevail, than in any other division of 
Prussia; and the Kiel rate (113), is higher than that of any Prussian 
town. 

1 Zeits. f. Hygiene, etc., Bd. xxxiii., 1900, S. 235. 

2 Deutsche med. Woch., March 6, 1902. 

3 " Medizinal-Stat. Mittheil., aus den k. Gesundheitsamte." 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 75 

It is least prevalent in the provinces bordering on Poland Posen (44), 
East Prussia (54), West Prussia (50), and Silesia (54) where the working 
classes are poor, comprising many Poles and Jews. 



Austria. 

In this country the cancer mortality has increased from 37 in 1880. 
to 70 in 1900 ; and coincidently there has been a great decline in the 
death-rates from phthisis and all kinds of tuberculosis. The tubercle 
rate is, however, still high viz., 349 for phthisis in 1903. 

The highest cancer death-rates are met with in the prosperous and 
well-to-do provinces of Salzburg (133), Upper Austria (115), Lower 
Austria (108), Tyrol and Vorarlberg (107) etc. ; and the lowest in the 
poor provinces of Bukowina (37), Galicia (28), and Dalmatia (19). In 
Bukowina and Galicia, Polish Jews comprise a large proportion of the 
population, and in Dalmatia there is a large Italian element. 

In Vienna the cancer rate increased from 107 in 1875, to 121 in 1900. 
With regard to tubercle, the mortality declined from 763 in 1872-1876, 
to 467 in 1897-1900. 



Hungary. 

As compared with Austria, Hungary is a poor country, with the 
phenomenally low cancer death-rate of 33, which in 1897 was only 26, 
and in 1903 it reached 39. The tubercle mortality of Hungary is the 
highest in Europe viz., 387 in 1903. 

The Buda-Pest cancer rate increased from 62 in 1896, to 72 in 1900, 
and the tubercle mortality has declined of late. 



Italy. 

Cancer is much less prevalent in Italy, which is a comparatively poor 
country, than in most European communities ; but even here the mor- 
tality has increased from 21 in 1880, to 52 in 1899, and to 58 in 1905. 

The tubercle death-rate is diminishing, but to a less extent than in 
most European countries, having fallen from 122 in the period 1897- 
1904, to 118 in 1905. 

The meat consumption per head (23 pounds in 1895) is the smallest 
of any European nation. 

The highest cancer rates are met with in the prosperous and well- 
to-do provinces of the north Tuscany (83), Emilia (78), Lombardy (71) 
etc. and it is here that the diminution in the tubercle mortality has 
been most marked. The lowest cancer rates are in the comparatively 
poor provinces of Apulia, Basilicata, and Calabria (30), while for Sardinia 
the phenomenally low rate of 19 is registered. 

For the chief towns the cancer rates are as follows : Florence, 137 ; 
Ravenna, 120 ; Milan, 101 ; Venice, 103 ; Rome, 77 ; Turin and Genoa, 59 ; 
and Naples, 56. 



76 THE NATUKAL HISTORY OF CANCER 



United States. 

With regard to extra-European countries, data are available for the 
United States, Australia, and New Zealand. 

In what follows in this section the reservation previously made, with 
regard to the peculiar difficulties under which vital statistics are com- 
piled in the United States, must be borne in mind. 

Such data as are forthcoming for the whole community show that 
the mortality from cancer and tumour increased from 9 per 100,000 living 
in 1850, to 29 in 1880, to 33 in 1890, and to 43 in 1900. The proportion 
of deaths from this cause to 1,000 deaths from all causes, increased from 
25-4 in 1890, to 32-9 in 1900. 

In the "registration area" alone, the "cancer and tumour" death- 
rate increased from 53 in 1890, to 65 in 1900. 

In the same limited area, the death-rate from cancer alone, increased 
from 47 in 1890, to 60 in 1900. 

There is no need to dilate upon the great increase in the riches, 
prosperity, and population of the United States during the nineteenth 
century, although it may here be remarked that, as in England, the 
wealth of the community is much less widely diffused among the 
population than in France, Switzerland, Denmark, and some other 
countries. 

Although urbanization has made great progress in the United States, 
the towns of 8,000 inhabitants and upwards having increased from 6 in 
1790, to 546 in 1900, nevertheless, two-thirds of the population still dwell 
in the country, and are mainly dependent upon agriculture. 

A diminishing tubercle death-rate has coincided with the increase of 
cancer, the tubercle rate having fallen from 245 in 1890, to 187 in 
1900. 

The meat consumption of the United States population, is consider- 
ably in excess of the European average. 

Cancer is much more prevalent in the northern than in the southern 
part of the United States, the chief centres being the wealthy commercial 
States of the Atlantic coast" and vicinity (51 to 41) and the Pacific States 
(51). The lowest rates are in the South Mississippi River belt (11), the 
south-west central region' (15), the southern interior plateau (18) etc. 
It is in these southern localities that the negro race is chiefly comprised ; 
and their cancer death-rate (47) is lower than that of the whites (66) ; but, 
even in southern States where negroes are rarely found, the cancer rates 
are very much below the average. 

For some of the chief cities of the United States, the following increases 
in the cancer death-rates have been recorded : New York, from 32 (1864) 
to 67 (1900) ; Chicago, from 32 (1880) to 63 (1900) ; Philadelphia, from 
31 (1861) to 70 (1904) ; Boston, from 28 (1863) to 85 (1903) ; Baltimore, 
from 18 (1864) to 63 (1903) ; New Orleans, from 15 (1864) to 82 (1903) ; 
and San Francisco, from 16 (1866) to 112 (1900). 



THE INCREASE OF CANCER, AND ITS CONCOMITANTS 77 



Australia. 

Thanks to the valuable publications of Adams, 1 Allen, 2 Mullins, 8 
Coghlan, 4 etc., we have fairly complete information as to the incidence 
of cancer in Australia during the last half-century. These data show 
steady increase of the disease, the death-rate per 100,000 living having 
been as follows : 14 (1851), 19 (1861), 25 (1871), 32 (1881), 45 (1891), 
and 57 (1901). 

Males have been relatively affected by this increase more than females. 
Thus, during the period 1870-1900, the male rate increased from 26 
to 59, whereas the augmentation for females was from 28 to 55 (Allen). 
A remarkable fact revealed by these data is, that the male cancer death- 
rate now exceeds the female rate ; and this holds as well for each of the 
constituent communities, as for the whole commonwealth. 

Some conception may be formed, as to the conditions of existence 
during the period to which these data refer, from the fact that it has been 
characterized by great increase and wide diffusion of material prosperity, 
by diminution of the tubercle and general mortality, by increase of 
insanity, by lessened birth-rate, by excessive consumption of meat, and 
by disproportionate increase of the capital towns. 

For the different divisions of the Australian Commonwealth, the fol- 
lowing progressive increases in the cancer rates have been recorded : 

New South Wales : 28 (1871-1875), 51 (1894), 57 (1900), and 65 (1903). 
For males, the rate increased from 18 (1860-1864) to 51 (1895-1899) ; and, 
for females, from 21 (1860-1864) to 50 (1895-1899). 

The phthisis death-rate declined from 92 (1871-1875) to 79 (1896- 
1898). 

Victoria : 32 (1871-1875), 61 (1891-1895), 72 (1900), and 76 (1903). 

The phthisis rate was 120 (1871-1875), 123 (1896-1898), and 111 (1903). 

Queensland : 17 (1871-1875), 35 (1891-1895), 46 (1900), and 49 (1903). 

The phthisis rate declined from 109 (1871-1875) to 93 (1896-1908), 
and to 78 (1903). 

South Australia : 20 (1871-1875), 47 (1891-1895), 59 (1900), and 72 
(1903). 

The phthisis rate was 89 (1871-1875), 87 (1896-1898), and 75 (1905). 

West Australia : 15 (1871-1875), 30 (1891-1895), 32 (1898), and 40 
(1905). 

The phthisis rate declined from 85 (1871-1875) to 75 (1896-1898), and 
to 65 (1905). 

Tasmania : 48 (1871-1875), 49 (1891-1895), 60 (1900). 

The phthisis rate declined from 101 (1871-1875) to 73 (1896-1898). 

While the average cancer death-rate for all Australia was 57 in 1900, 
or 5 per cent, of the total mortality from all causes, in the capital cities 
the cancer death-rate was 81, or 6-4 per cent, of the total mortality ; 

1 Lancet, 1904, vol. i., pp. 423, 498. 

2 Australian Medical Gazette, April 21, 1902, p. 169. 

3 Ibid., January 20, 1896. 

4 Ibid., April 21, 1902, p. 174 ; eee also his " Wealth and Progress of New South 
Wales," 1894. 



78 THE NATURAL HISTORY OF CANCER 

whereas, in the rural districts, the cancer rate was only 44, or 3-9 per 
cent, of the total deaths from all causes. 

I have previously referred to the greatly increased proclivity to 
cancer experienced by British immigrants in Australia, of which the 
latest Australian vital statistics afford some striking evidence. Thus, 
for 1900, while the cancer death-rate of native-born Australians was only 
22, the corresponding rate for the British-born was 203 ; and, for other 
foreign-born persons, as follows : French, 375 ; Austrian, 300 ; Scandi- 
navian, 289 ; and German, 252. In 1895, Mullins found that of the 
British-born, in Australia, 1 in 966 died of cancer, as against 1 in 7,746 of 
the native-born white Australians. These rates are much in excess of 
those prevalent in the immigrants' native countries. 

Even when the figures have been corrected for age differences, the 
same result is shown ; for, taking persons aged thirty-five years and 
upwards, 58 per 100,000 living of the Australian-born died of cancer, as 
against 137 of the British and foreign-born. 

Dr. MacDonald, of Dunedin, believes that this proclivity is mainly 
due to the gluttonous habits of the immigrants in respect to meat- 
eating : " Meat for breakfast, lunch, dinner, tea, and supper, just like 
the porridge-pot in Scotland." 

Even the Chinese in Australia suffer severely from cancer, for their 
mortality from this cause, in 1900, amounted to 72 per 100,000 ; and of 
1,316 Chinese deaths registered in Victoria in 1894-1900, 42 were due to 
this malady. 

With regard to the Australian aborigines, however, who in 1891 
numbered about 60,000, Allen notes : that " cancer is rare among them, 
many years often passing without a single case being registered, although 
they are not really exempt from either external or internal cancer." 

Among the Pacific Islanders, employed in Queensland, Roth reports 
that, during the last eleven years, he has never seen or heard of a single 
case of cancer ; and several other medical men have testified to the same 
effect. 

New Zealand. 

In these islands the conditions of existence much resemble those 
current in Australia ; and the proclivity to cancer is much the same in 
the two countries, the New Zealand rate having increased from 32 (1877- 
1888), to 44 (1891), to 60 (1900), and to 71 (1903). Taking 100 as the 
standard, the cancer mortality for males in the last twenty years increased 
to 367, as against 260 for females. The phthisis rate declined from 87 
(1871-1875), to 75 (1900), and to 69 (1903). In New Zealand, as in 
Australia, the birth-rate and the general mortality have declined, while 
insanity has increased. British immigrants are much more prone to 
cancer, than the native-born white New Zealander ; but, the aborigines 
are seldom affected. 



CHAPTER IV 
THE TOPOGRAPHICAL DISTRIBUTION OF CANCER 

IN every part of the world the incidence of cancer presents well-marked 
topographical variations, to many of which I have referred in the fore- 
going chapters ; but the importance of the subject seems to demand 
more detailed consideration. 

C. H. Moore 1 was the first to study these variations for England and 
Wales. He showed that the disease was more prevalent in London and 
its vicinity, in the southern and eastern counties, than elsewhere ; and 
that it was least prevalent in the north-western and northern counties, 
and in Wales. If, he says, the country be divided by a line drawn from 
Bristol to Peterborough, the mortality from cancer in the southern 
divisions is considerably in excess of that on the north of the line. In 
the year 1861, for instance, one of every thirty deaths of females in the 
south-eastern division was due to cancer ; while in the north-western 
division, the proportion was only 1 to 59, or about one-half. Moore 
gives the following instructive data (see table, p. 80). 

Some years later the same subject was thoroughly reinvestigated, 
with due allowance for diversities in age and sex distribution, by Havi- 
land, 2 and Moore's results were in every respect confirmed. 

The districts having the highest cancer mortality (4 to 6 per 10,000 
living) comprised London, the south-eastern and eastern counties ; 
those with the lowest mortality (3 to under 2 per 10,000 living) 
were the north-western counties, Monmouth, and Wales ; between these 
extremes were the northern, midland, and south-western counties, with 
a cancer death-rate of from 3 to 4 per 10,000 living. 

These investigations comprised the decennia 1851-1860 and 1861- 
1870 ; and, although in the intervening period, the cancer mortality 
was shown to have everywhere increased, yet those localities having 
the highest, lowest, and medium cancer rates were the same for 
both periods. 

In the Forty-seventh Annual Report of the Registrar-General, this 
subject received official attention. The subjoined table (see p. 81) from 
this source, shows the mean annual cancer mortality per standard million 

1 " Antecedents of Cancer," London, 1865, p. 41. 

2 " Geographical Distribution of Disease in Great Britain," 2nd edit., 1892 ; 1st edit., 

1875. 

79 



80 



THE NATURAL HISTORY OF CANCER 





1851. 


1861. 


1851-1860. 




One Cancer 
Death to 


One to 
Total 


One Cancer 
Death to 


One to 
Total 


One 

Death ! 


One Death 
from Can- 


Divisions. 


Population. 


Deaths. 


Population. 


Deaths. 


from 
Cancer 


cer in 
Total Fe- 




i 


Female. 




I 


i 


1 


i 


Female. 


in Fe- 
males 
aged 35 
to 64. 


male Mor- 
tality 
between 
Ages 35 
to 64. 


London 


4884 


1778 


113 


38 


3758 


1553 


95 


34 


67 


12 


S. -Eastern : ^ 






















(Surrey, Kent, 1 
Sussex, Hamp- j 
shire, Berkshire )) 


5362 


2206 


105 


41 


4419 


1697 


86 


30 


83 


12 


South-Midland: A 






















(Middlesex, 






















Herts, Bucks, 






















Oxfordshire, 
Northampton, 


4304 


2163 


87 


42 


3520 


2141 


72 


41 


89 


13 


Huntingdon- 






















shire, Beds, 






















Cambridgeshire) _ 






















Eastern : ^1 






















(Essex, Sussex, J- 
Norfolk) J 


7226 


2131 


150 


42 


4553 


1713 


98 


34 


84 


12 


S.-Western : ^ 
(Wilts, Dorset, 1 
Devon, Somer- j 
set, CornwaU) J 


4921 


2343 


103 


45 


4309 


1920 


85 


34 


100 


14 


W.-Midland: ^ 






















(Gloucestershire, 






















Herefordshire, 






















Shropshire, Staf- 


7478 


2470 


177 


55 


5057 


2175 


109 


42 


90 


u 


fordshire, 






















Worcestershire, 






















Warwickshire) , 






















N.-Midland : * 






















(Leicestershire, 






















Rutland, Lines, 


6417 


2692 


131 


54 


4499 


2329 


96 


47 


97 


14 


Notts, Derby- 






















shire) 






















N.-Western : 






















(Lancashire, 


7946 


3263 


214 


80 


6249 


2454 


166 


59 


103 


20 


Cheshire) 






















Yorkshire : 






















(West, East, 
and North 


5881 


2869 


141 


65 


4634 


3068 


110 


45 


100 


16 


Ridings) 






















Northern : 






















(Durham, 






















Northumber- 
land, Cumber- 


5454 


2970 


119 


60 


3983 


2258 


92 


49 


102 


16 


land, West- 






















morland) 






















Wales : ^ 






















(North, South, 1 
and Mon- j 


7166 


3833 


149 


74 


4282 


2962 


92 


59 


137 


20 


mouthshire) J 






















England and "I 
Wales / 


5846 


2461 


133 


52 


4484 


2019 


101 


41 


91 


15 



THE TOPOGRAPHICAL DISTRIBUTION OF CANCER 81 



aged twenty-five and upwards, in the registration divisions during the 
thirty years 1851-1880 : 



' 1 


Males. 


Females. 


Persona. 


London 


736 


1463 


1117 


South-Eastern . . ... 


557 


1207 


898 


South-Midland . . ... 


597 


1148 


886 


Eastern 


502 


1175 


855 


West-Midland 


519 


1133 


841 


Yorkshire 


511 


1114 


827 


Northern . . ... 


565 


1041 


815 


South-Western . . ... 


555 


1043 


811 


North- Western . . ... 


523 


1055 


802 


North-Midland . . ... 


496 


1074 


799 


Wales 


538 


841 


697 


England and Wales (average) 


561 


1444 


867 



It will be seen that the results brought out by this table, are prac- 
tically identified with those previously elicited by Moore and Haviland. 

In the supplement of the Fifty-fifth Annual Report of the Registrar- 
General, a somewhat similar table for the counties is given for the 
decennium 1881-1890 x ; but, in this case, the mortality is for persons aged 
thirty-five years and upwards. 

The counties with the highest rates were : 





Males. 


Females. 


Persons. 


London 


1784 


2667 


2250 


Huntingdonshire 


1916 


2373 


2157 


Cambridgeshire . . . 


1666 


2323 


2012 


Sussex 


1491 


2454 


1999 


Warwickshire 


1533 


2373 


1976 



Those with the lowest rates were : 





Males. 


Females. 


Persons. 


Lancashire 
Durham 
Staffordshire 
Rutlandshire 
Worcestershire 
South Wales 
Cornwall 
Wilts 


1275 
1227 
1234 
1429 
1213 
1352 
1380 
1122 
1038 
1129 
1143 
1157 

1397 


2092 
2117 
2048 
1874 
2048 
1911 
1855 
2036 
2098 
2095 
1967 
1948 

2261 


1706 
1696 
1663 
1663 
1653 
1647 
1630 
1604 
1597 
1578 
1578 
1574 

1844 


Derbyshire 


Buckinghamshire 
Dorsetshire 
Monmouthshire 

England and Wales (average) 



1 In the preceding decennium (1871-1880) the highest cancer rates for persons aged 
twenty-five years and upwards were in London (1269), Cambridgeshire (1193), Northamp- 
tonshire (1138), Huntingdonshire (1138), Sussex (1137), and Warwickshire (1095) 5 and 
the lowest rates were in Lancashire (944), North Wales (933), Dorset (929), Monmouth- 
shire (925), Cornwall (917), Durham (898), Hertfordshire (895), Buckinghamshire (881), 
South Wales (873), and Derbyshire (839). 



82 



THE NATURAL HISTORY OF CANCER 



The highest and lowest death-rates for all ages corrected for age and 
sex distribution for the same decennium, were met with in the following 
counties: the highest were in Huntingdonshire (916), Cambridge- 
shire (789), Devonshire (786), North Wales (736), Sussex (727), Nor- 
folk (716), London (683) ; and the lowest were South Wales (501), Mon- 
mouthshire (482), Derbyshire (482), Lancashire (477), Staffordshire (475), 
and Durham (440). 

In the registration divisions, the cancer death-rates per million living 
of all ages and both sexes, in 1884, and in 1900, were as follows : 







1884. 
. 650 .. 


South-Eastern 
South-Midland 
Eastern 
West-Midland 




. 622 . . 
. 694 . 
. 763 . 
. 595 . 
. 536 . 


Northern 
South-Western 
North-Western 
North-Midland 
Wales 




. 442 . 
. 642 . 
.. 490 . 
. . 520 . 
. . 533 . 



1900. 
964 
883 
929 
895 
863 
809 
816 
950 
773 
798 
775 



560 



England and Wales (average) . . 

In the counties, the highest and lowest rates per million living at all 
js for 1890, 1900, and 1901 were as follows : 





1890. 
Both Sexes. 


1900. 
Both Sexes. 


1901. 
Males. 


1901. 
Females. 


Huntingdonshire 


1108 


1083 


964 


1300 


Cambridgeshire 


939 


1033 


951 


1330 


North Wales 


871 


1063 


981 


1200 


Devonshire 


847 


964 


818 


1121 


Norfolk 


781 


991 


879 


1132 


Suffolk 


779 


991 


790 


1031 


Derbyshire 





783 


519 


932 


South Wales 


563 


658 


577 


798 


Lancashire 


555 


730 


593 


905 


Staffordshire 


538 


685 


482 


802 


Durham 


518 


619 


497 


804 


Monmouthshire 


504 


606 


576 


789 


England and Wales (average) 


676 


828 


691 


985 



The general outcome of these data, which cover the whole of the last 
half of the nineteenth century, is to show the accuracy of Moore's con- 
clusions as to the local incidence of the disease. 

Another important indication furnished by them is, that the increase 
of the disease has involved the whole of the country, in such a manner 
that those divisions and counties, which formerly had the highest, lowest, 
and medium cancer rates, for the most part, still retain their peculiarities 
in these respects, although the incidence of the disease has everywhere 
augmented. 

But, although the local incidence of the disease is thus shown to be 
remarkably persistent ; yet, in several cases, changes in the comparative 



THE TOPOGRAPHICAL DISTRIBUTION OF CANCER 83 

proclivity of certain localities have occurred ; thus, North Wales, where 
the cancer mortality was formerly much below the average, is now 
subject to a high rate ; and this change seems to have coincided with 
the invasion and settlement of the locality by well-to-do immigrants from 
the large towns of Lancashire and the Midlands, with their industrial, 
wealth-producing innovations etc. 

The foregoing data refer exclusively to the death-places of cancer 
patients, which, of course, may not correspond with their birth-places. 
By noting the birth-places of 352 cancer patients, I was able to ascertain 
that the localities where the highest cancer mortality obtains, are also 
the localities where most cancer patients are born thus confirming 
Nunn's research on the same subject. 1 

It is a matter of importance to determine the part played in the 
causation of these local variations in the cancer mortality, by differences 
in the age and sex distribution of the population ; and the Registrar- 
General has lately published data that enable corrections of this kind 
to be made. Although the accuracy of the general results indicated by 
the crude death-rates is not impugned by these corrections, yet the 
comparative mortality of individual counties inter se is often disturbed ; 
thus, while the crude cancer death-rate of Huntingdonshire to that of 
Durham (1881-1890), was as 208 to 100, the corrected ratios are as 127 
to 100 yet the former county, after correction, still retains its status as 
one of those districts where cancer is most prevalent, and the latter as 
one of those where it is least so. 

Corrected for age and sex diversities, the counties with the highest 
cancer rates are London, Huntingdonshire, Cambridgeshire, Sussex, 
Warwickshire etc. ; while those with the lowest rates are Monmouth- 
shire, Derbyshire, Durham, Staffordshire, Lancashire, South Wales, 
Dorset, Bucks, Wilts, Cornwall etc. 

It is thus evident that there are topographical variations in the 
incidence of cancer, which are quite independent of age and sex diver- 
sities ; and, it may also be added, of the disturbing influence caused by 
the presence of large hospitals. 

Hence, it is exceedingly improbable that the higher cancer mortality 
of the agricultural, as compared with the industrial population, can be 
explained as the result of any of the above-mentioned disturbing factors, 
although such certainly exist. 

In like manner, the average age of the Irish population is much higher 
than that of either England or Scotland, and the proportion of elderly 
women it contains is also greater, owing to the large numbers of elderly 
people left behind after the younger ones have emigrated ; yet, the cancer 
mortality of Ireland is much less than that of either England or Scotland, 
which clearly shows that inequalities in the incidence of cancer mortality 
are determined by other considerations besides those of age and sex 
distribution. 

According to Haviland, 2 these variations are entirely due to geo- 
logical configuration and its consequences. 

1 For further details vide my work on " Diseases of the Breast," 1894, p. 256. 

2 Op. cit. 

62 



84 THE NATURAL HISTORY OF CANCER 

He maintains that the regions of highest cancer mortality are low- 
lying districts, traversed by, or contiguous to, rivers that seasonally flood 
the adjacent riparial lands ; whereas the lowest cancer mortality is found 
in high and dry sites, where floods do not occur, and where the subsoil 
consists of hard, non-retentive rocks e.g., English lake district or of 
absorbent substances like chalk and oolite. In support of these views, 
he instances the Thames and its tributaries, which run through a vast 
cancer-field ; and he points to the only localities in the Thames Valley 
the Orsett and Dartford districts where there is a low cancer mortality, 
as being just those spots where the chalk crops out. 

In favour of the opinion that, in this country, cancer is specially pre- 
valent in flat, low-lying, fenny districts, there is, I think, much to be 
said. The Forty-seventh Report of the Registrar-General shows that 
Cambridgeshire and the adjacent counties of Northamptonshire, Hunting- 
donshire, and Bedfordshire, all have a very high cancer mortality. Lin- 
colnshire and Essex figure less prominently in this Report ; but my analyses 
show that the number of cancer patients born in these localities is exceed- 
ingly high. This state of things is known to have existed ever since 
statistical records have been kept. In the decennial Report (1881-1890), 
the Registrar-General writing on this subject says : " Crude death-rates 
show that in and around Huntingdonshire and Cambridgeshire, there is 
a well-defined area in which cancer is exceptionally prevalent. It com- 
prises the districts of Stamford, Bourn, Spalding, and Holbeach in Lin- 
colnshire ; Oundle and Peterborough in Northamptonshire ; and most of 
the counties of Huntingdonshire and Cambridgeshire. In 1881-1890 this 
area had a mean population of over 300,000, its crude cancer rate being 
857 per million, or 46 per cent, above the average rate for the country in 
general ; in the preceding decennium the excess was 44 per cent." 

Nevertheless, I am unable to accept Haviland's views as a sufficient 
explanation of the topographical variations in the distribution of cancer. 
All low-lying and seasonally flooded districts have not a high cancer 
mortality. The very large area drained by the Severn and its tribu- 
taries, for instance, is shown by the Registrar-General's Forty-seventh 
Report, to have a low average cancer mortality. 

Moreover, islands that have no rivers, that are not low-lying, and 
that are not of alluvial formation, nevertheless have a high cancer mor- 
tality ; such are the Scilly and Channel Islands, and the Isle of Wight 
may also be mentioned in this connexion. 

The Scillies are small and rocky throughout, their total population 
being about 2,000 ; but, during the decennium 1881-1890, their cancer 
death-rate was considerably higher than that for all England, and still 
more was it in excess of that for the adjacent mainland (Cornwall). 

The cancer death-rate for these islands, per 10,000 living, for the 
decennium (1881-1890) was 7-6 (males 2-9, females 12-2), the corre- 
sponding figures for aU England and Wales being 5-8 (males 5-8, and 
females 7-3). 

For the Isle of Wight, the cancer death-rate, in 1900, was 9-4 per 
10,000 living, or 1 in 16 of the total mortality. 

A Jersey practitioner having informed me that cancer was very 



THE TOPOGRAPHICAL DISTRIBUTION OF CANCER 85 

prevalent there, as well as in Guernsey, I wrote to the gentleman who 
furnishes the mortality statistics such as they are for Jersey, to the 
Registrar-General ; but failed to elicit a reply. 

Similar conditions are met with in many inland districts ; thus, 
Dr. Borrowman, of Elie, in Fifeshire, N.B., writes to me : " It will interest 
you to know that cancer is very common here. Between 11 and 12 per 
cent, of my patients have died from malignant disease. This is a par- 
ticularly dry part of the country. There are no rivers at all in the 
district ; and the few streams that do exist have a good fall. Flooded 
land is quite unknown here." 

In other countries this peculiarity has also been noted ; thus, cancer 
is very prevalent in the Ballarat gold-field region of Victoria, where no 
rivers, no alluvial valleys, and no malaria occur, the whole country being 
a volcanic plateau, from which the rain drains away as soon as it has. 
f alien, i 

Recently attempts have been made by the microbists, to explain these 
topographical variations as the outcome of contagion ; but, the peculiar 
manner in which this malady is distributed throughout the whole country, 
and the constancy with which the various local incidence ratios have been 
maintained from decennium to decennium, notwithstanding the universal 
increase, tells against this theory, the general inadequacy of which I shall 
subsequently have occasion to point out . 

It appears to me that the explanation of these variations must be 
sought, in the conditions of life peculiar to the respective populations. 

Let us now carefully examine the vital statistics of our country for 
the last half-century, in order to determine the particular conditions 
which have tended to this end. Such an examination shows as I have 
previously indicated that the cancer mortality is lowest where the 
struggle for existence is hardest, the density of population greatest, the 
tubercle mortality highest, the birth-rate highest, the average duration 
of life shortest, the infantile and general mortality highest, and where 
sanitation is least perfect in short, among the poor of the industrial 
classes in our large towns ; whereas, among the wealthy and well-to-do 
where the standard of health is at its best, and life is easiest, and all the 
conditions of existence are just the converse of the foregoing and among 
the agricultural community, there the cancer mortality is highest. 
Other things being equal, there are, in my opinion, no more potent 
factors in the causation of cancer than high feeding and easy living. 
Hence it is that the cancer mortality of mining and industrial centres, 
like South Wales, Monmouthshire, Lancashire, Durham, Derbyshire, 
Staffordshire, Cornwall, West Riding, etc., is so low ; and that it contrasts 
so favourably with the cancer mortality of the generality of agricultural 
districts. Although the ratio of pauperism in the rural districts is quite 
double that of the industrial ones, I have no hesitation in saying, as the 
result of my own observation of life under both conditions, that so far 
as food and comfort are concerned, the average agricultural labourer is 
much better off during his working years than his confrere of the industrial 
army. As a proof of this, it may be mentioned that the average duration 
1 J. H. Well, Lancet, vol. ii., 1901, p. 976. 



86 THE NATURAL HISTORY OF CANCER 

of the agricultural labourer's life, is more than double that of his mate 
in the large towns ; and his wages and general conditions of existence 
have greatly improved during the last half-century. On this subject a 
leading London newspaper remarked : l " The material prosperity of the 
agricultural labourer is, and has been, during recent years, higher 
than at any period during the last century. The slight falling-off in the 
amount of his wages is more than compensated for by their increased 
purchasing power. All the necessaries of life, during the last thirty years, 
have become much cheaper meat, bacon, cheese, tea, sugar, butter, 
and coal the difference being something like 25 per cent, in favour of 
the buyer." 

Provincial towns with the highest cancer death-rates per 100,000 
living, during the decennium 1881-1890 are : Chichester (118), Canter- 
bury (113), Bala (107), Huntingdon (106), Exeter (101), Saffron-Walden 
(99), Cirencester (97), Cambridge (95), St. Asaph (94), Dolgelly (94), 
Buckingham (94), Bath (93), Scarborough (93), Holbeach (92), Devizes 
<91), Bury St. Edmunds (90) etc. 

It is -noteworthy that this list does not include a single great industrial 
-centre, the places named being well-to-do, easy-going, residential country 
towns. 

For the great industrial centres the rates are much less, viz., Bristol 
(83), Birmingham (72), Liverpool (69), Manchester (67), Leeds (62), New- 
castle (55), Derby (52), Sheffield (50), Salford (48), Wolverhampton (47), 
Cardiff (45), West Ham (40), Bolton (40), Blackburn (38), Durham (32) 
etc. 

In London and its vicinity, where the wealth of the nation is clotted, 
there the cancer mortality is highest ; and it is significant that this 
mortality is highest of all in those parts of the metropolis and its suburbs, 
where the well-to-do most abound. Thus, for 1903, the highest cancer 
rates were in wealthy Hampstead, Marylebone, Chelsea, and Westminster ; 
while the lowest were in the poor industrial districts of Bermondsey, 
Stepney, Bethnal Green, Poplar, and in the poverty-stricken extra-metro- 
politan district of West Ham. Crude rates show, that the disease is 
very much more prevalent in the former than in the latter group of com- 
munities. Corrections for age and sex diversities, for hospitals and other 
public institutions, although they somewhat mitigate these extremes, still 
show that the cancer mortality is much less in the poor industrial districts, 
than it is in those inhabited by the wealthy and well-to-do. Moreover, 
a similar state of things is noticeable in all our large towns (as I have 
previously indicated in the case of Bristol), and throughout the country 
in general. 

In other European countries, where sufficiently detailed statistics 
have been kept, similar topographical variations in the incidence of the 
disease are everywhere noticeable. 

1 Standard, August 12, 1897. 



CHAPTER V 
CANCER AND OTHER TUMOURS IN ANIMALS 

Some General Remarks on Tumours in Animals. 

CONSIDERING the great advances lately made in most branches of biology, 
the stagnation of comparative pathology is a surprising and regrettable * " 
anomaly ; for, many of the most important pathological problems now <**/'< 
pending, might be more profitably investigated by this method, than by \\ 
the experimental or other dispersive analytical procedures, now so much ,>. 
in vogue. ft* 

Although progress has lately been made, the comparative pathology 
of tumours is still in a rudimentary and backward condition. 

Some important conclusions have, however, already been estab- 
lished. 

Morphological and physiological processes being similar in the animal 
world and in mankind, it is only reasonable to suppose that pathological 
processes will also manifest a certain similarity ; and, from what is 
known of the diseases of animals, this supposition appears to be fully 
justified, at any rate, so far as tumours are concerned, it has been 
ascertained that the analogy holds good. 

In vegetable organisms, physiological and pathological processes are 
certainly much less complex than in animals, if only in that the former > 
are destitute of nerve and lymph- vascular systems, which add so much 
to the difficulty of disentangling the genesis of vital processes in the 
latter. 

As I have shown in my book on the " Principles of Cancer and Tumour 
Formation," which was published in 1888, the really fundamental physio- 
logical and pathological processes are the same in plants as in animals ; 
and it accords with this, as I have indicated in the above-mentioned 
work, that malignant and other tumours also originate in vegetable 
organisms. 

We thus arrive at the important conclusion, that tumours may arise, 
under certain circumstances, in any multicellular animal or vegetable 
being. ; 

Another consideration to which I have previously called attention is, J-H?" 
that these abnormalities very rarely affect organisms living in a state of ^/ 
nature. It is almost exclusively among domesticated varieties, among 
those that have been kept long in confinement, or that have been other- 
wise abnormally circumstanced, that tumours are met with ; thus, in 
savages and wild animals, tumours very rarely occur. 

87 



88 THE NATURAL HISTORY OF CANCER 

Nearly all of those who have specially studied the comparative inci- 
dence of tumours in animals and mankind, are agreed that these maladies 
are relatively infrequent in the former ; and this appears to me to be due 
to the fact, that animals have been much less extensively subjected to 
the influence of domestication, and to such other abnormal conditions of 
existence as I have above referred to, than mankind. At any rate, it is 
remarkable that nearly all the examples of animal tumours hitherto 
reported, have been met with in our common domesticated species. 

Recent observations as to the relative frequency of malignant tumours 
in the latter, show that these maladies are not so rare as was formerly 
believed : thus, Veterinary-Inspector Trotter found that of 47,362 cattle, 
slaughtered at Glasgow in 1903, 131 had some form of malignant tumour, 
or 2-8 per 1,000, the corresponding ratio for English humanity being 
about 60 per 1,000. 

All the indications at present available point to the great rarity of 
cancer in wild animals, whether living in confinement or under natural 
conditions ; indeed, but very few instances of this kind have so far been 
reported. 

Of 2,647 wild mammals comprised in the New York Zoo, during a 
period of five years, H. Brooks * reports that not a single specimen of 
tumour was met with, although they were specially examined ad hoc. 
A large proportion of these animals had only recently been reduced to 
captivity. Of those which died, 744 were submitted to thorough post- 
mortem examination ; yet, only a single case of malignant tumour was 
found, viz., sarcoma of the ovary of a wild, white, racoon-dog (Nyctereutes 
albus), from the north of Japan, which sickened and died emaciated after 
a sojourn of two years in the Zoo. 

Under these circumstances, it seems to me that the dictum of the 
Cancer Research Fund 2 as to the incidence of cancer in animals approxi- 
mating in frequency to that in mankind must be rejected, as being with- 
out scientific warrant. 

In respect to such conditions as the foregoing, there is some analogy 
between the incidence of tumours and developmental anomalies ; for the 
latter, like tumours, are relatively rare in savages and wild organisms ; 
whereas, they are common in mankind, in domesticated organisms, and 
in those that have been kept long in confinement, or that have been 
otherwise abnormally circumstanced. 

In this connexion, I must call attention to another noteworthy con- 
comitant of the augmented British cancer mortality, viz., the great 
increase in the incidence of congenital defects and premature births, as 
to which I shall subsequently have to refer more in detail. 

Thus, whatever the causes of malignant tumours may be, they are 
not limited to mankind as John Hunter, Camper, Otto, and some other 
pathologists believed nor even to the animal world, as most modern 
pathologists even now suppose. 

From such facts as have already been ascertained with regard to 
tumours in animals, it may be confidently predicted, that all the varieties 

1 American Journal of Medical Science, May, 1907, p. 769. 

2 Scientific Reports of the Imperial Cancer Research Fund, No. 2, part i., 1905. 



CANCER AND OTHER TUMOURS IN ANIMALS 89 

of the neoplastic process recognized in mankind have their counterparts 
in the animal world. 

It appears to me that the chief feature in which animal tumours 
differ from their human congeners, is in respect to the relative frequency 
of site incidence ; and this I suspect is mainly the outcome of diversity 
of function and structure in certain organs, which, in their turn, ulti- 
mately depend upon differences in habit and mode of life for such influ- 
ences are as potent in pathology, as in physiology. 

In the first place, it is noticeable that the connective-tissue type of 
malignant tumour, which in mankind comprises only from 6 to 15 per 
cent, of all malignant growths, in animals is at least as frequent as the 
epithelial form, and some pathologists consider that it is more frequent. 

Johne found, as the result of post-mortem examination, that sarco- 
mata comprised 47 per cent, of the total tumours met with in horses, 
37 per cent, in cattle, and 28 per cent, in dogs ; while the corresponding 
figures for malignant epithelial tumours were, 22 per cent, for horses, 
8 per cent, for cattle, and 52 per cent, for dogs. 

With regard to the site incidence of malignant tumours in animals, as 
compared with human beings, the most striking fact is the comparative 
rarity of these tumours in many localities, where they are of very frequent 
occurrence inhumanity e.g., the stomach, liver, uterus, intestine, tongue, 
and mouth. 

The comparative rarity of gastro-intestinal types of cancer in animals 
is very marked ; thus, 1,312 cases of cancer in common domestic animals 
(horse, ox, dog, sheep, cat, and pig), as tabulated by Sticker * (1,170 cases), 
Bashford, McFadyean, Cadiot and Roger, comprise only twenty instances 
of malignant disease of the stomach, or about 1-5 per cent. ; whereas, for 
human beings, the corresponding figure is about 17 per cent. : in like 
manner, the same series comprises only 42 cases of malignant disease of 
the liver, or 3-2 per cent. ; whereas, in mankind, the corresponding per- 
centage is about 13-5. The only form of gastro-intestinal malignant 
disease at all common in these animals, is that which affects the anus, of 
which there were 97 examples, or 7-4 per cent., a figure greatly in excess 
of the corresponding human ratio, for I have found that only 0-37 per 
cent, of human cancers are thus situated. This anal form of malignant 
disease is of more frequent occurrence in the dog, than in any other of 
the animals mentioned ; for, of 738 canine cancers, Sticker found that 89, 
or 12 per cent., were thus located. 

The rarity of lingual cancer in these animals may be judged from the 
fact, that only four examples are comprised in the 1,312 cases, or 0-3 per 
cent. ; to these may be added 16 cases of cancer in the mouth (chiefly 
of the gums). Thus, we get 20 cases of cancer of the tongue and mouth, 
or 1-5 per cent., the corresponding figure for humanity being 3-5 per 
cent. 

Only 26 cases of uterine malignant disease all from Sticker's list 
are comprised in these 1,312 cases, or about 2 per cent, of the total, the 
corresponding figure for humanity being about 12 per cent. 

By way of contrast with the foregoing, mammary cancers are of 

1 Arch. f. klin. Chir., 1902, Bd. Ixv., pp. 616, 1023. 



90 THE NATURAL HISTORY OF CANCER 

' commoner occurrence in these animals than in mankind ; for, of the 1,312 
animal tumours, no less than 360 were thus located, or 27-4 per cent., 
the corresponding figure for humanity being only 8 per cent. This 
frequency of mammary cancer in these animals, is due to the great pre- 
ponderance of this form in dogs, as shown by Sticker's list, which com- 
prises 341 cases of canine mammary cancer in a total of 738 malignant 
tumours in dogs, or 46 per cent. 

Cutaneous manifestations of the disease comprise 16 per cent, of the 
animal series, this localization being of very frequent occurrence in dogs ; 
whereas, in humanity, skin cancers comprise only about 2-5 per cent, of 
the total cases. 

According to Johne, most sarcomata in animals originate from the 
bones. 

It will be gathered from the foregoing, that the usual seats of traumata 
and mechanical injuries, rarely coincide with the site incidence of malignant 
tumours in animals. 

With regard to the sex incidence of the disease in animals, there is a 
dearth of really satisfactory data ; but, available indications point to the 
conclusion that there is no such great diversity between the sexes in this 
respect, as is the case with humanity ; and from this it may be inferred, 
that the greater proclivity of the human female is due rather to circum- 
stances connected with her special sheltered environment, than to any 
peculiarity directly connected with sex. It accords with this, that 
malignant tumours are of common occurrence in castrated domestic 
animals of both sexes. 

It has been suggested that the immunity of animals from uterine 
tumours malignant or otherwise as compared with humanity, may in 
some way be due to the absence of menopause, in which they differ from 
human females. 

In humanity, as I shall subsequently have occasion to show, the 
characteristic feature of the age incidence of cancer, is not as is generally 
believed its increase with advance of years ; but, rather, its dispropor- 
tionate augmentation in the post-meridian periods of life the liability to 
the malady waxing as the developmental and reproductive activities wane. 

In the animal world, the age incidence of cancer is governed by a 
similar law, tumours of this kind being very rare in early life, commonest 
in post-meridian ages, and less frequent in advanced age, as Sticker's 
data show ; thus, of 134 dogs affected with malignant tumours, he 
found that only one was young, 107 were middle-aged, and 26 were 
extremely old etc. 1 

Very few instances of congenital malignant tumours in animals are 
known to me, but Penberthy 2 has met with sarcoma of the chest wall 
in a newly born foal ; and Crisp has seen a large encephaloid tumour on 
the chest of a lamb. 

1 Of 70 dogs with malignant epithelial tumours, the ages were as follows : 2 to 3 years 
in 14'3 per cent. ; 5 to 6 years in 25 per cent. ; 7 to 8 years in 28 per cent. ; 9 to 10 years 
in 20 per cent. ; 11 to 15 years in 1T4 per cent. Of 90 horses similarly affected, the age 
percentages were as follows : under 4 years old 2'2 ; 5 to 6 years 4'2 ; 7 to 8 years 10 ; 
9 to 10 years 15'5 ; 11 to 12 years 9 ; 13 to 14 years 11 ; 15 to 16 years 17'7 ; 17 to 18 
years 12'2 ; 19 to 20 years 14 4 ; 23 to 25 years 5'3. 

2 Journ. Comp. Path., etc., 1902, vol. xv., p. 271. 



CANCER AND OTHER TUMOURS IN ANIMALS 91 

Examples of tumours, malignant and otherwise, have now been 
demonstrated in all classes of vertebrata ; and although at the present 
time the pathology of the invertebrata is practically terra incognita it 
seems probable that in the future similar tumours will be shown to occur 
in this division also ; indeed, a beginning has already been made, for 
J. W. Williams * has described an instance of a pediculated tumour, com- 
prising muscular and glandular elements, in a fresh- water mussel (Ano- 
donta cygnea), and similar tumours have been noted by Collinge. 2 Ryder, 3 
in an oyster, has also met with a large tumour ; and, as is now generally 
recognized, the formation of pearls is due to a formative process excited 
by the presence of some foreign body, often a parasite. Invertebrate 
animals are also very prone to pseudo-plasms, caused by parasitic 
sporozoa etc. 

The very frequent occurrence of malignant tumours in castrated 
animals of both sexes shows, that ablation of the essential sex glands 
has no deterrent power whatever on the onset of this malady, but there 
are rather indications that these mutilations favour its development ; 
thus, nearly 50 per cent, of the horses affected with cancer in Sticker's 
list, had been castrated. 

In the animal world, even more than in mankind, malignant tumours 
are apt to be confounded with various pseudo-plasms of "chronic in- 
flammatory," tuberculous, microbic, aspergillary, or of unknown infec- 
tive origin ; and, mistakes of this kind are all the more prevalent, because 
the comparative pathology of animals has hitherto been but little studied. 
As an example of this, reference may be made to Wehr's 4 experiments 
as to the transmissibility of " cancer " from dog to dog, which attracted 
so much attention a few years ago ; the so-called " cancer " in this case 
being nothing but a previously unrecognized kind of venereal pseudo- 
plasm of unknown aetiology, but certainly not cancerous. 

In all probability the present hasty identification of " Jensen's 
tumour" which is transmissible from mouse to mouse with cancer, is 
destined to furnish another memorable example of the saine kind of 
mistake. 

According to Rayer 5 and Leblanc, among the older comparative 
pathologists, carnivorous animals are more prone to malignant tumours 
than herbivorous ones ; whereas, with regard to tubercle, the relative 
liability is just the converse. In support of this contention Raye^r found 
that cancer was common, and tubercle rare, among birds of prey ; while, 
among non-carnivorous birds, tubercle was the prevalent malady, and 
cancer was unusual. In support of this observation, it may be men- 
tioned that Rayer's contemporary, E. Rousseau, found that eagles and 
vultures, confined in the Jardin des Plantes at Paris, not infrequently 
succumbed with cancer. 

Among those who have lately investigated this subject, Johne, Woods 
Hutchinson, Schutz, Pick and Poll, support Rayer's view. 

1 Journ. of Anat., 1890, vol. xxiv., p. 307. 

2 Ibid., 1891, vol. xxv., p. 154. 

3 Proc. Acad. Nat. Sci., Philadelphia, U.S., 1887. 

4 Arch. f. klin. Chir., 1889, Bd. xxxix., S. 226. 
6 Arch, de med. comparee, 1843. 



92 THE NATURAL HISTORY OF CANCER 

In this connexion, it is significant that among our common domestic 
animals, malignant tumours are of much more frequent occurrence in 
dogs, than in any others ; thus, of 1,312 cases of malignant tumours in 
domestic animals tabulated by Sticker etc., no less than 810 were in 
dogs. Cats are also very liable to cancerous tumours. 

In the animal world tubercle is a common disease, especially with 
our domesticated bovines and birds. 

All of these facts, as well as others to which I have already referred, 
indicate the important part played by the conditions of existence in 
determining the incidence of cancer ; and, among these conditions, nutri- 
tion is one of the most important. In my opinion, Dr. Bashford showed 
extraordinary lack of understanding of biological principles and scientific 
insight, when he wrote i 1 " The great diversity of food, habit, and condi- 
tions of life generally in animals in which cancer occurs, shows that such 
external agencies have no causative influence." 

With regard to non-malignant tumours, it is noticeable that exostoses 
and osteomata are very common in all classes of vertebrata, even in 
reptiles and fishes. Papillomata are also of frequent occurrence in 
animals. Adenomata are comparatively rare, except in the mamma of 
dogs. Fibrous and fatty tumours are also extremely rare in animals, 
wild or domesticated. When we recollect that most of our domestic 
animals have been bred for thousands of years, with special reference to 
fattening, this rarity of fatty tumours is all the more remarkable. 



Monkey. 

X Great interest attaches to the maladies of monkeys, because it is 
among the highest members of this order that we find the nearest approach 
in organization to mankind. 

Notwithstanding the immense number of these creatures constantly 
under observation in the zoological collections of Europe, it is a curious 
fact that only about half a dozen examples of tumours have hitherto 
been reported, and their comparative immunity from this kind of malady 
seems to be a reality. 

Thus, some time ago, Bland-Sutton 2 examined the bodies of 110 of 
these animals which had died in the London Zoo, but not a single example 
of any tumour did he find. Subsequently, H. J. Campbell 3 made thirty- 
eight similar post-mortem inspections, with the like negative result. 

Leblanc, 4 however, long ago reported that he had met with instances 
of malignant tumours in monkeys, and I expect that they do occasionally 
occur ; but I can cite only two modern instances. 

The first of these is due to Goodhart, 5 who found " cancer " of the 
pituitary body in an Anubis baboon, from the London Zoo, where the 
animal had long been a familiar denizen. The tumour a large, ragged- 

1 Second Annual Report Imperial Cancer Research Fund, 1904. 

2 Lancet, 1883, vol. ii., p. 276. 

3 Guy's Hospital Reports, 1891, vol. xlviii., p. 19. 
* Clin. Vet., August, 1843, p. 343. 

6 Transactions of the Pathological Society, London, 1883, vol. xxxvi., p. 36. 



CANCER AND OTHER TUMOURS IN ANIMALS 93 

looking object occupied the pituitary fossa, which it had eroded, and 
some of the adjacent structures were infiltrated. Histologically it com- 
prised " large epithelial- like cells arranged in some sort of an alveolar 
manner." There were no secondary deposits. This tumour, together 
with the brain and skull, are preserved in the museum of the Royal 
College of Surgeons. 

The second instance was met with in a bonnet monkey, only eight 
months old, by Bland-Sutton, 1 the tumour being an intra-ocular glioma, 
consisting chiefly of small round cells. 

Here also mention may be made of a curious atypical epithelial 
growth of the cervix uteri of a monkey by Woods Hutchinson, 2 who was 
in doubt whether it was an adenoma or a carcinoma. 

In this connexion reference may be made to the attempts of Shattock 
and Ballance, Metchnikoff, and others, to transmit human cancer experi- 
mentally to monkeys, all of which experiments failed. 

Thus, monkeys, like human savages, seem to have very little pro- 
clivity to cancer. 

Here it may be remarked that the alimentary propensities of these 
animals are predominantly frugivorous, but a good many of them are 
not averse to animal food when they can get it. Some kinds are insecti- 
vorous, and others feed upon almost anything they can get. As with 
mankind, many species have a singular liking for birds and their eggs, 
as alimentary dainties. 

With regard to non-malignant tumours, the available data are 
exceptionally meagre. 

Bland-Sutton has met with an instance of leio-myomatous thickening 
in the uterus of a baboon, which had some resemblance to myoma ; and 
the same observer has also seen a fatty tumour-like mass in the vicinity 
of each testis of a monkey with hermaphroditic malformation. 

According to Otto, exostosis is not uncommon at the tip of the tail 
of long-tailed monkeys ; and, in the museum of the Royal College of 
Surgeons of Ireland the hand of a monkey is preserved, showing a spongy 
exostosis of the first phalanx of the little finger. 

Monkeys are also subject to hydatid cysts. M 

These few examples practically exhaust our present knowledge of 
non-malignant tumours in monkeys. 

It is an ancient belief that monkeys in captivity are very prone to 
tubercle ; and, some years ago, a mild sensation was experienced when 
Bland-Sutton 3 flatly contradicted this cherished conception. In justifica- 
tion of his contention, he appealed to the record of 110 post-mortem 
inspections of monkeys, which had died in the London Zoo, and comprised 
only three instances of tubercle. He found, however, that these animals 
had experienced very heavy mortality from diseases of the lungs the list 
comprising 22 examples of bronchitis, 11 of pneumonia, etc. 

Some years later H. J. Campbell, 4 as the result of similar work in the 
same field, arrived at exactly the opposite conclusion, having found that 

1 Journ. of Anal, and Physiol., 1885, vol. xix., p. 449. 

2 " Human and Comparative Pathology," 1901, p. 258. 

3 Lancet, 1883, vol. ii., p. 276. * Op. cit. 



94 THE NATURAL HISTORY OF CANCER 

tuberculous disease was very frequent in these monkeys. Thus, no less 
than 20 of the 38 bodies he examined, presented well-marked tuberculous 
lesions. In addition to these, there were also many cases of broncho- 
pneumonia. 

It is evident that these discrepancies depend mainly upon diversity 
as to the criterion of tubercle. Viewing the matter in this light, we shall 
probably be right in maintaining the validity of the old belief. 

In support of this, reference may be made to the observations of 
Dr. A. J. Harrison, 1 who has long been connected with the management 
of the fine collection of animals at the Clifton Zoo. He says : " Monkeys 
are very liable to chest affections, and there can be no question that 
we have lost a great many from tuberculous disease of the lungs. They 
seem very prone to pleurisy, and adhesions are frequently found with 
and without tuberculous masses in the lungs ; but actual cavities do not 
seem to be frequent. Monkeys seem to be particularly prone to tubercle." 

It accords with the foregoing, that Lydia Rabinowitsch 2 has lately 
found many examples of tubercle among the monkeys that died in the 
Berlin Zoo ; and, of 36 cases in which these lesions were specially examined 
ad hoc, in nearly three-fourths the type of tubercle was human, examples 
of bovine, avian, and mixed types being only occasionally met with. 

It has likewise been proved that monkeys are very susceptible to the 
experimental inoculation of both the human and bovine forms of tubercle, 
as the experiences of Dieulafoy, Krishaber, Dungern, and others testify. 

Of like import is the common occurrence of specimens of simian 
tuberculous disease in museums, such as that of the Royal College of 
Surgeons of Ireland, which have good collections illustrative of the 
pathology of these animals. 

According to Woods Hutchinson, 3 monkeys in their native forests 
are but little prone to tubercle ; but, in captivity, it is difficult to procure 
specimens free from the disease. Thus, of 45 monkeys that died in 
captivity at the London Zoo (1898-1899), 17 died of tubercle, or 38 per 
cent. Food habits have much to do with tubercle mortality ; for, of 
Hutchinson's animals, 35 were vegetarian Catarrhines, and it was among 
these that all the 17 deaths occurred ; whereas, not one of the ten deaths 
among the Platyrrhine monkeys, who had taken a fair amount of animal 
food, was due to tubercle. 

Dog. 

Of all domesticated animals, dogs are by far the most prone to malig- 
nant tumours ; thus, of 60,471 canine patients at the Berlin thierartz- 
lichen Hochschiile (1886-1894), Frohner* found that 2,871 had some 
form of tumour, of which 1,154 were cancerous, or 1-9 per cent, of the 
total ; of 1,306 dogs examined, Sticker 5 reports tha,t 72, or 5-5 per cent., 
had cancer ; while, according to Semmer.e of 3,525 dogs examined at his 
clinic, 8 per cent, were cancerous. 

1 Bristol Med. Chir. Journ., 1894, vol. xii., p. 285. 

2 Deutsche med. Woch., May 31, 1906, S. 866. 

3 " Human and Comparative Pathology," 1901. 

4 Monats. f. prakt. Thierheilkunde, 1895, Bd. vi. 

6 Arch. f. klin. Chir., 1902, Bd. Ixv., p. 616 et scq. 

"Lehrb. d. allgem. Chir. u. Operatioiislehre " (Moller), 1893. 



CANCER AND OTHER TUMOURS IN ANIMALS 95 

These figures indicate that cancer is even more prevalent among dogs, 
than among human beings. 

All the chief types and varieties of cancer met with in mankind, also 
prevail among dogs. Epithelial and sarcomatous forms are common. 
Melanotic and myxomatous varieties also occur ; and a form of disease, 
" presenting the histological features of rodent ulcer," has also been seen. 
Malignant tumours containing heterotopic structures cartilage, bone 
etc. are common. Leukaemia also occurs. 

According to Johne, of 93 tumours found post-mortem in dogs, 28 
per cent, were sarcomatous. 

Most of the affected animals are domestic pets ; but, as previously 
mentioned, Brooks has met with sarcoma of the ovary, in a wild racoon- 
dog, that had been kept for two years in captivity. Three-quarters of 
these animals were from five to ten years old ; and Frohner says he has 
never seen a malignant tumour in a dog under two years old. 

Sticker's analysis of 738 cases of canine cancer, shows that the com- 
monest seats of the disease are the mamma (45 per cent.), skin (21 per 
cent.), anus (21 per cent.), liver (3 per cent.) ; and, less frequently, the 
kidney, testis, penis, prostate, eye, bladder, vagina, lung, thyroid, ovary 
etc. Very remarkable is the great rarity of gastric cancer, of which 
there was only one instance ; the intestine provided not a single example ; 
and in only two cases was the uterus affected. 

Of the malignant mammary tumours of female dogs, those of the 
epithelial type predominate ; thus, of 18 tumours of this kind, histo- 
logically examined by Cadiot and Roger, 1 11 were glandular epithelio- 
mata, and 7 were sarcomata. Other interesting series of malignant 
mammary tumours have been reported by Ortschild, 2 Cornil and Petit, 3 
and MacFadyean. 4 

The usual type of malignant epithelial tumour of the dog's mamma, 
resembles that which is so frequent in the breast of the human female 
the acinous varietv predominating ; but tubular forms are also met with, 
which are often associated with cysts and intra-cystic papilliferous growths, 
as in humanity. Acute and chronic varieties of the disease also occur, 
and the colloid form has also been reported (Gibbes). Melanotic mammary 
cancer has been noted (Crisp etc.). In short, every variety of mammary 
cancer that has been discriminated in mankind, may be matched in the 
dog. The hindermost glands of the series are most prone to be affected. 
Male dogs have relatively greater proclivity to mammary cancer, than X 
male humanity. 

In dogs, these malignant mammary tumours are much more fre- 
quently associated with gross heterotopia cartilaginous, osseous, cal- 
careous formations etc. than are the corresponding tumours of humanity. 
G. Petit 5 has lately published a good study of the pathology of these 
canine " mixed tumours." 

With regard to mammary sarcomata, these are relatively of more 

1 " Bouchard's Traitede Path. Gen.," 1895, t. i. 

2 Johns Hopkins Hosp. Butt., 1905, vol. xvi., p. 185. 

3 Butt, et Mem. Soc. Anat. de Paris, 1905, t. Ixxx., p. 137. 
* Journ. of Comp. Path., etc., 1890, vol. iii. 

6 Bull., etc., de la Soc. Anat. de Paris, 1906, No. 5, p. 373. 



96 THE NATURAL HISTORY OF CANCER 

^C frequent occurrence in canine than in human pathology ; and they also 
are very much more frequently associated with gross heterotopia : Cadiot 
and Roger found structures of this kind in five out of seven specimens 
examined. Cystic and adenoid formations are as common as in the 
corresponding human tumours ; and, as in the latter, spindle-celled 
elements predominate. Alveolar, melanotic, and myxomatous forms of 
the disease have also been met with. 

vy Of the numerous attempts by Ortschild, Gratia, and Lienaux, to 
transmit these tumours by implantation to other dogs, all were unsuc- 
cessful. 

Of non-malignant mammary tumours, adenoma, fibroma, enchon- 
droma, osteoma, papilloma, and cystoma have been reported. 

Mammary fibro-adenomata are not uncommon in female dogs, and 
Ortschild has described an instance of the same malady in a male. These 
tumours also are fairly often associated with heterotopic elements, such 
as bone and cartilage, of which Rolleston x has studied examples. 

An interesting case of villous papilloma was some time ago seen by 
J. W. Sibley 2 "A multilocular cystic tumour, with villous intra-cystic 
growths, from the mamma of a bitch " and Ortschild has lately met 
with a similar case. 

Enchondromatous and osteoid tumours of the mamma of female dogs 
are comparatively common, as was long ago shown by Lebert, J. Miiller, 
Virchow, etc., and modern instances of this kind have been studied by 
Adams, Langlois, Go wing etc. 

Several examples of malignant disease of the normally placed and of 
the ectopic testis in dogs have been recorded ; as also of cancer super- 
vening after injuries ; thus, in a setter dog, Birchmore saw sarcoma 
form after a gunshot wound of the jaw. 

With regard to the reputed frequency of malignant disease in the 
anus and its vicinity, which is a special feature of the neoplastic pathology 
of the dog, it is evident that this matter requires further investigation. 
It is already knoAvn, however, that a benign adenomatous tumour not 
uncommonly develops in this vicinity probably from the circum-anal 
scent-glands the exact nature of which is still sub judice. These tumours 
are circumscribed, lobulated, and easily shelled out ; histologically they 
consist of solid cylinders of epithelial cells which are sometimes pig- 
mented regularly arranged in delicate vascular connective tissue. 
Tumours of this kind have been known to recur after removal (Mac- 
Fadyean, 3 Wallace 4 etc.) ; and it is believed that one form of malignant 
disease of the anus arises from this source. 

Anal cancers of the epidermoidal type also occur. 

G. Petit 5 has given an interesting account of several cases of " bran- 
chiogenic " cancer of the neck in dogs. 

Among the non-malignant tumours met with in these animals, 
reference may be made to fibromyomata of the uterus, of which instances 

Transactions of the Pathological Society, London, 1897, vol xlviii., p 324 

Ibid., 1858, vol. xi., p. 460. 

Practitioner, April, 1899, p. 460. 

Transactions of the Pathological Society, London, 1896, vol. xxxviii., p. 659. 

Bee. de Med. Vtt., 1902, p. 673. 



CANCER AND OTHER TUMOURS IN ANIMALS 97 

have been reported by Keiffer,i Wagner,2 E. H. Williams and Hobday ; 3 
and, in the vagina, similar tumours have been found by Aulton and Hob- 
day, 4 Leisering etc. 

Cases of ovarian cystomata have also been recorded in veterinary 
publications ; and a tumour of this kind has been known to attain a 
weight of 15 pounds. 

Examples of adenoma of the liver (Schweizer and others), of the 
kidney (Jung), and polypoid adenoma of the trachea (Bid well), are also 
on record. 

Cavernous angioma of the liver has been seen by Petit and Virchow. 

A big fibrous tumour, which contained osteoid deposits, from the 
popliteal space of a large dog, is comprised in the pathological collection 
of the Hunterian Museum (No. 800). 

A large retro-peritoneal lipoma has been seen by A. J. Williams 5 
and by L. Hudson. 6 Ortschild 7 met with a similar tumour in the para- 
vaginal region ; and also in the left pectoral region the latter animal being 
also affected with a malignant " mixed " tumour of the mamma. 

A bony growth, connected with the cervical vertebrae, has been 
described by Viborg. 

Branchial cysts have been met with by G. Petit and others, while 
Cathelin has seen a cyst connected with the small intestine, and Orts- 
child cystic hygroma of the shoulder. 

Solid and cystic goitrous tumours also occur, of which many cases 
have been recorded (Morell Mackenzie, Faris etc.). 

Papillary cutaneous excrescences are of common occurrence ; warts 
also occur in the mouth and on the foot-pads of dogs. 

In a subcutaneous fibroid swelling, Lefas found included epidermoidal 
structures ; and Petit 8 has seen a branchial dermoid cyst of the neck. 

Several instances of dermoid hairy patch on the ocular conjunctiva 
have also been described (Dobson, Taylor etc.). 

Besides the contagious venereal growths previously referred to, dogs 
are also prone to contagious papillomata of the mouth, which are trans- 
missible by artificial means, and resemble the " sublingual tumour " of 
human nurslings as described by Riga and Fede. 

Dogs are comparatively speaking but little prone to tubercle; yet 
tumour-like swellings due to this cause, to pseudo-tubercle, actino- 
mycosis, streptothrix and other mycotic infections are met with. Pick and 
Poll have found quasi -maMgn&nt gastric tumours, due to the presence of 
Spiroptera sanguinolata, a small parasitic nematoid worm. Hydatids 
also occur. Examples of quasi-malignant tumours, caused by the 
injection of cultures of various microbes, are elsewhere referred to. 9 

In further illustration of the subject of canine malignant tumours, 
the following additional references may be useful : 

Bull, de la Soc. Beige de Oyn. et d'Obstet., 1900, t. x., p. 231. 
Cent. Bl. f. attg. Path., etc., 1905, vol. xvi., Heft 4. 
Journ. of Comp. Path.,' 1902, vol. xv., p. 267. 

Veterinary Journal. May, 1905, p. 255. 

Veterinarian, June, 1897, p. 301. 

Transactions of the Pathological Society, London, 1890, vol. xli., p. 401. 
Op. tit. 8 Bee. de Med. Vet.. 1905, No. 4, p. 60. 

Chapter X. 



98 THE NATURAL HISTORY OF CANCER 

Six cases of cancer of the breast, with inoculation experiments, by 
Gratia and Lienaux ; l cancer of mamma of a bitch, by Monsarrat ; 2 three 
cases of cancer of the axillary sweat-glands, by Creighton ; 3 melanotic 
cancer of the mamma of a terrier bitch, with dissemination in the lungs, by 
Crisp ; 4 cystic chondro-sarcoma of the mamma of a bitch, by Rolleston ; 5 
cysto-sarcoma proliferans of the mamma of a greyhound, with secondary 
formations in the liver and spleen, and cystic disease of the ovaries, by 
Bertolet ; 6 chondro-osteo-sarcoma of the mamma of a bitch, by Virchow ; 7 
cases of retro-peritoneal and peri-tracheal sarcoma in young dogs, by 
Spencer ; 8 cases of cystic myxo-sarcoma of the neck, by Creighton ; 9 " un 
cas de chondro-sarcoma intestinal generalise au poumon," by Petit; 10 
cancer of prostate, by De Rouville ; u columnar epithelioma of lung, by 
Silcock; 12 cystic sarcoma of the testis of an Italian greyhound; 13 melanotic 
sarcoma of the immediate vicinity of the scrotum in a Welsh terrier, by 
Leon ; 14 similar disease from the foot of a dog ; 15 " myxo-sarcomatodes 
medullare " of the vagina, by Kaschewarowa-Rudnewa ; 16 fibro-spindle- 
celled sarcoma of the intestine, with invasion of the great omentum and 
mesenteric glands, by Petit ; 17 sarcoma of the palate of an otter-hound, 
by Lediard ; 18 osteo-sarcoma of the thigh, by G. Petit ; 19 sarcoma of the 
olfactory lobe, by Marchand and Petit ; 20 cases of Hodgkin's disease, by 
MacFadyean ; 21 lymphomatous tumours of the spleen, by H. V. Williams 22 
etc. 

Cat. 

Judging by the comparative paucity of published cases, cats are much 
less prone to malignant tumours than dogs ; but, according to the records 
of the Veterinary Pathological Institute of Berlin, this is not so ; for of 
34 cats there examined, 2, or 5-9 per cent., were thus affected. The usual 
primary seats of the disease in cats are the mamma and skin ; other parts 
liable being the lung, pleura, liver, tongue, ovary, penis, eye, anus, lip 
etc. Most of the malignant forms of epithelial and connective-tissue 
tumours, including the melanotic, have been reported in cats. Carcino- 
matous tumours of the mamma of the acinous and tubular types are met 

1 "Ann. de Med. Vet.," Bruxelles, 1894. 

2 Liverpool Med. Chir. Journ., 1900, vol. xx., p. 132. 

3 Transactions of the Med.-Chir. Society, London, 1882, vol. Ixv., p. 53. 
1 Transactions of the Pathological Society, London, 1848, vol. ii,, p. 346. 

5 Ibid., London, 1897, vol. xlviii., p. 324. 

6 Philadelphia Medical Times, U.S., 1872-1873, vol. iii., p. 315. 
" Wiirzburger Verhandl.," Bd. i., S. 137. 

8 Transactions of the Pathological Society, London, 1891, vol. xlii., p. 472. 

9 Journal of Anatomy, vol. xiv., p. 292. 

10 Butt. Soc. de Med. Vet., Paris, 1905, vol lix , p 283 

11 Butt. Soc. Anat., Paris, July, 1896. 

12 Transactions of the Pathological Society, London, 1886, vol. xxxvii., p. 570. 
" Catalogue Hunterian Museum. Path. Suppl.," p. 71 (No. 4,235). 

14 British Medical Journal, 1899, vol. ii., p. 1046. 

1 " Catalogue Hunterian Museum," Path. Series, No. 469A. 
18 Arch. f. path. Anat., 1872, Bd. liv., S. 73. 

17 Butt. Soc. Anat., Paris, 1899, p. 487. 

18 Transactions of the Pathological Society, London, 1888, vol. xxxix., p. 458. 

19 Ike. de Med. Vet., February, 1906, p. 81. 

20 Butt. Soc. Anat., Paris, 1906, No. 5, p. 397. 

21 Journ. of Comp. Path., etc., 1903, vol. xvi., p. 379. 
Journal of Medical Eesearch, 1902, vol. vii., p. 408. 



CANCER AND OTHER TUMOURS IN ANIMALS 99 

with ; among those who have recently studied specimens of this kind 
are Petit, 1 Leiden, 2 Spencer, 3 and Eva Field. 4 

The last named has also described an example of cystic round-celled 
sarcoma of the subcutaneous tissue below the ear ; and Breton and Petit 5 
a case of intra-ocular sarcoma of the globe of the eye ; while Stroud 6 has 
met with sarcoma of the ovaries and pelvis. 

There is a specimen of cancellous exostosis of the lower jaw in the 
Hunterian Museum ; 7 and a similar formation connected with the upper 
part of the femur is in Guy's Hospital Museum. The Hunterian Museum 
also exhibits the omentum of a cat studded with small, stalked, fibro-fatty 
outgrowths ; and angiomata of the liver has also been noticed. 

An example of sublingual ranula has been seen by Ridler and Hobday, 8 
and the same authors have also reported a case of nasal polypus. 

Like other carnivorous animals, cats are but little prone to tubercle. 



Horse. 

Malignant tumours in horses are decidedly rare, for, according to 
Sticker, of 215,037 of these animals under treatment at the Berlin 
" Hochschule " Veterinary Clinic, only 103 were thus affected, or 0-046 per 
cent. However, many cases are on record in the veterinary journals ; and 
of Sticker's 1,170 tabulated cases, 318 were in horses. 

The commonest primary seats of the disease are : the antrum and the 
adjacent naso-oral cavities 9 (16 per cent.), the penis (16 per cent.), 
kidney (9 per cent.), skin (7 per cent.), lung and pleura (5-6 per cent.), 
bladder 10 (4-4 per cent.), testis (4 per cent.), eye (4-4 per cent.) ; and in 
lesser degrees of frequency, the vulva, gum, stomach, anus, mamma, 11 
uterus, vagina, intestine, ovary, larynx, tail 12 etc. 

Not a single example of malignant disease of the tongue is comprised 
in the 356 cases in horses, tabulated by Sticker, MacFadyean, Bashford, 
Cadiot and Roger ; and it is noticeable that gastric, intestinal, and uterine 
malignant tumours, are exceedingly rare in these animals. 

The melanotic form of tumour disease is of common occurrence in 
horses, especially in those of white, grey, roan, and dun tints ; but even 
the black varieties are not exempt. Its commonest seats are the anus, 
root of the tail, external genitals, skin etc. Most formations of this 
kind are of a chronic nature, and comparatively benign these are 
described by Cornil and Trasbot 13 as fibromata ; but occasionally they 

Butt., etc., Soc. Anat., Paris, 1905, t. Ixxx., p. 137. 

Zeits. f. klin. Med., 1904, vol. Hi., p. 409. 

Transactions of the Pathological Society, London, 1890, vol. xli., p. 400. 

Journal of American Medical Association, December 29, 1904, p. 983. 



Pec. de Med. Vet., Paris, 1902, t. ix., p. 38 

17. 

talogue," vol. iii., p. 12. 
Journal, June, 1905, p. 3 
, the cheek being the pa 
vol. xvi., p. 161. 



eternary ourna, une, 1, p. . 

" Path. Catalogue," vol. iii., p. 12. 

Veterinary Journal, June, 1905, p. 333. 

9 For a case, the cheek being the part affected, vide Journ. of Comp. Path., 1903, 
xvi., p. 161. 

10 Case by MacFadyean, Journ. of Comp. Path., 1902, vol. xv., p. 148. 

11 For a case, vide Journ. of Comp. Path., 1903, vol. xvi., p. 161. 

12 Case by MacFadyean, Journ. of Comp. Path., 1902, vol. xv., p. 148. 

13 " De la Melanose," 1868. 

72 



100 THE NATURAL HISTORY OF CANCER 

manifest all the properties of malignancy, with widespread dissemina- 
tion, and are then generally described as being of sarcomatous structure, 
spindle cells predominating. Melanotic tumours sometimes attain great 
size, weighing as much as from 20 to 60 pounds ; and some remarkable 
instances of their heredity are cited by Virchow. 1 Lebert 2 mentions a 
case in which a black tumour, that had long existed under the root of the 
tail at length became generalized, thousands of small tumours forming in 
the lungs, liver, peritoneum, pericardium, spleen, and in many other 
parts. The Royal College of Surgeons Museum in London contains two 
interesting specimens of this malady prepared by Hunter : 

1. No. 290, Pathological Series : " A section of the tail of a horse, and 
of a large, lobulated, soft, pale brown and black tumour, embedded deeply 
in its substance, and projecting in lobes and lobules on its surface." 

2. No. 291, Pathological Series : " Melanotic tumour removed from 
the neck of a horse. It is black throughout, firm, lobulated, and loosely 
encapsulated (10 by 5 inches). It was removed by Hunter from the 
inner side of the jugular vein, which passed over it." 

A good example of the malignant form of melanosis, with widespread 
dissemination, has been described by Hutchinson. 3 Bloodgood 4 has met 
with the same disease in the liver, and G. Petit 5 within the spinal canal. 

A specimen of intra-ocular melanoma, which filled the whole globe, 
and had involved also the orbit, is contained in the Hunterian Museum 
(No. 2,259, Pathological Series). 

Epidermoidal cancer of the membrana nictitans, with dissemination, 
has been described by MacFadyean ; 6 and instances of epidermoidal 
cancer of the ocular conjunctiva by Petit and Coquot, 7 and by Taylor. 8 

Malignant tumours are of specially frequent occurrence in gelded 
animals ; thus, of seven examples of epidermoidal cancer of the penis 
in MacFadyean' s list, all were from geldings. 

Instances of epithelioma of the penis have been studied by Patteson, 9 
and Webber, 10 of the vulva by Petit, 11 and of the vagina by Bashford. 12 

Of 128 tumours found post-mortem in the horse, Johne found that 
60, or 47 per cent., were sarcomatous. 

An example of " alveolar sarcoma " of the upper jaw has been pub- 
lished by Pike ; 13 and veterinary museums generally contain specimens of 
" spina ventosa " of this locality, most of which are due to sarcomatous 
tumours. Malignant epithelial tumours, mostly of the epidermoidal 
type, also arise from the antrum. 

, l " Path, des Tumeurs," 1869, t. ii., p. 236. 

" Traite des Mai. Cancereuses," p. 159. 
3 Archives of Surgery, 1890, vol. iv., p. 48. 
* Johns Hopkins Hospital Bull., June, 1905, p. 239. 

5 Bull, et mtm. Soc. Anat., Paris, 1905, No. 5, p. 382. 

6 Journ. of Comp. Path., 1904, vol. xvii., p. 352. 

7 Bee. de Mid. Vet., 1905, t. Ixxxii., No. 1, p. 10, with excellent clinical and histo- 
logical figures. 

8 Royal London Ophthalmic Hospital Reports, 1876, vol. ix., p. 74. 

9 Illustrated Medical News, December, 1888, p 220 

10 British MedicalJournal, 1899, vol. ii., p. 882. 

11 Bee. de Med. Vet., Paris, 1902, vol. ix., p. 118. 

12 Proceedings of the Royal Society, London, 1904, vol. Ixxiii. 

13 British Medical Journal, 1896, vol. i., p. 989. 



CANCER AND OTHER TUMOURS IN ANIMALS 101 

Sarcomatous tumours of the lower jaw have been reported by Lediard * 
and Waldmann ; 2 while many examples of " spina ventosa " of this bone 
are to be found in veterinary museums. 

Actinomycetic tumours of the naso-oral region, which are of common 
occurrence in horses, require to be discriminated from malignant tumours 
of this vicinity, which they often closely simulate. 

Sarcomatous tumours growing from the ribs, ulna, etc., have also 
been met with. 

Several cases of leukaemia, and of intra-thoracic lumphadenoid disease 
have been recorded (Petit, Weil etc.). * 

Malignant disease of the retained testis has been seen by Axe 3 and 
others; while several cases of ossifying chondro-sarcoma, and of carcinoma, 
of this organ are on record (Gamgee etc.). 

Examples of intra-ocular and orbital sarcoma are referred to by Axe ; 
and there is a specimen of this kind in Guy's Hospital Museum. 

Several specimens of mammary carcinoma in the mare have been met 
with (MacFadyean, Cadiot and Roger etc.) ; and a large cystic fibro- 
adenomatous tumour of this part in a mare, which comprised ossifying 
and chondromatous structures, and was of "a quasi-carcinomatous 
nature in some parts," has been described by Scott. 4 

Eight instances of cancer of the uterus, 7 of the vagina, 4 of the 
ovary, and 8 of the stomach, are included among Sticker's 318 malignant 
horse tumours ; and Bland-Sutton has seen 2 cases of uterine sarcoma. 

An example of ulcerated cancer of the skin behind the ear, which was 
ascribed to the irritation of a papillary excrescence by the bridle, has 
been met with by Birchmore ; 5 and Woods Hutchinson has seen sarcoma 
of the lip of a horse. 

I have previously referred to Penberthy's case of congenital sarcoma 
of a foal. 

-Judging by the numerous specimens of exostoses and osteomata con- 
tained in the chief museums, horses must be very prone to these forma- 
tions. I have references of growths of this kind connected with the 
spine, pelvic bones, inferior maxilla, ribs, sternum, scapula, humerus, 
cannon bone, gluteal aponeurosis, palate, nasal septum, etc. 

Ivory exostoses of the skull bones, like those met with in human 
pathology, also occur ; and a tumour of this kind, as big as a man's fist, 
has been known to have been shed spontaneously from the nostril of a 
horse. Loose bony and cartilaginous tumours have also been found in 
the knee-joint. 

Many instances of exostoses due to ossification of the tendons of 
muscles, have also been met with. 6 

Some remarkable instances of odontomata and dentigerous so-called 
" cranial dermoids " have been described by Broca, 7 chiefly from speci- 

Transactions of the Pathological Society, London, 1884, vol. xxxv., p. 468. 

Zeits.f. Thier-med., 1899, Bd. iii., S. 199. 

Veterinarian, vol. xxv., p. 262. 

Veterinarian, July, 1895, p. 462. 

New York Medical Journal, 1883, vol. xxxviii., p. 659. 

For references to cases, vide Barrier, Pec. de Med. Vet., 1905, t. Ixxxii., No. 6, p. 115. 

" Traitedes Tumeurs," 1869, t. ii., chap. x. 



102 THE NATURAL HISTORY OF CAXCER 

mens in the celebrated Alfort and other veterinary museums. Aberrant 
teeth in horses have also been noted in the palate bone, and more rarely 
in the petrous bone ; and probably some of these odontomata arise from 
redundant, aberrant tooth germs. 1 

A peculiar kind of symmetrical hyperostosis of the maxillary bones 
of West African horses and mules recalling the affection known as 
" goundrou," which occurs among the negroes of the Ivory Coast has 
been studied by Zieman 2 ; and Ridewood 3 exhibited not long ago at the 
Linnean Society a specimen of a similar condition, bu the regarded the 
symmetrical bony bosses as indications of a pair of rudimentary horns ! 

Horses are liable to fibrous and papillary growths ; while sebaceous 
cysts and horny excrescences have also been noted. 

Virchow,4 R. W. Smith, 5 A. Thomson, 6 and De Boinville,? have 
reported instances of multiple fibro-neuromata in horses and other 
domesticated animals. 

In the body of an old mare, sent to the Clifton Zoo to be slaughtered 
as food for the carnivora, Harrison 8 found an enormous fibro-myomatous 
tumour of the uterus ; and Virchow had previously called attention to 
tumours of this kind, in the uterus and vagina of horses and other animals. 

A large fibro-myomatous tumour of the duodenum of a mare, which 
had caused fatal intestinal obstruction, has been described by Cadeac 9 
extensive areas of the tumour being in a state of fatty degeneration. 

A good many instances of polypoid adenomatous tumours of the 
intestine projecting within the gut, have also been found. An ossified 
tumour of this kind of the caecum, has been reported by G. Petit, 10 who has 
also met with a similar growth in the rectum, which was undergoing 
calcification ; 1X and peri-anal adenomatous tumours also occur. 

Several instances of pedunculated so-called fatty tumours connected 
with the small intestine, which had caused fatal intestinal obstruction, 
have also been recorded in veterinary publications ; and these tumours are 
generally referred to as overgrown appendices epiploicse ; but, in the light 
of Cadeac's case, some of them may be otherwise derived. 

To such sources as the foregoing, many of the foreign bodies often of 
considerable size found free in the peritoneal cavity, may be referred. 

Large intra-abdominal fatty tumours have also been met with in 
horses and other domesticated animals (Fiirstenburg). Hobday 12 has 
seen lipoma in the undescended testis, which specimen is now preserved 
in the Hunterian Museum ; and MacFadyean has seen two examples of 
subcutaneous lipoma of the fore-leg. 

1 Ridler, " Dentigerous cyst in the vicinity of the ear of a Mare, which contained 
two odontomatous masses, one of great size," Journ. of Comp. Path., etc.. 1902, vol. xv., 
p. 266 ; also Hobday, ibid., vol. xii., p. 174. 

2 Journal of Tropical Medicine, London, May 1, 1905, p. 135. 

3 Proceedings of the Linnean Society, October, 1904, p. i. 
" Path, des Tumeurs," t. iii., p. 496. 

" Sydenham Society's Atlas. Illust. Path.," fasc. xi. 

6 'Neuroma and Neuro-fibromatosis." Edinburgh, 1900. 

7 Veterinary Journal, March. 1905. p. 130. 

8 Bristol Med. Chir. Journ., 1894, vol. xii., p. 288. 

9 tec. de Med. Vet., March 15, 1885. 

10 Butt, et mem. Soc. Anat., Paris, January, 1902. 

11 Rec. de Med. Vet., 1905, No. 6, p. 122. 

12 Transactions of the Pathological Society, London, 1906. 



CANCER AND OTHER TUMOURS IN ANIMALS 103 

Ovarian and parovarian cysts are not unknown ; and a tumour of this 
kind has been reported, which weighed as much as 84 pounds. 

Ovarian dermoids are also found; and, in a case of this kind by Pollock, 1 
in addition to piliferous pigmented skin, the tumour contained cartila- 
ginous and ossifying structures. 

Tumours of somewhat similar composition have also often been found 
in connexion with the testis, especially during castration. 2 

Dermoid cysts, sometimes containing teeth, have been met with in 
the temporal, petrous, and sphenoid regions ; while Leblanc 3 has seen an 
intra-cranial piliferous dermoid. 

Horn-like cutaneous outgrowths often occur in horses. 

Spencer 4 has reported a case of polycystic disease of both kidneys, so 
diffused that hardly any normal renal structure could be seen. 

Cysts of the unobliterated urachus have been met with in horses, 
cows, pigs, etc. 

Horses are singularly liable to the formation of large intra-cerebral 
tumours, in connexion with the choroid plexuses the so-called " psam- 
moma "; or, by reason of their richness in cholesterine, " cholesteatoma," 
of which examples have been reported by McCarthy, 5 Saundby, 6 Mac- 
Fadyean 7 etc. 

A unique case of rhabdo-myoma of the subcutaneous shoulder region, 
has been described by Monod, 8 in which the tumour was attached by a 
long thin pedicle to the scapula. 

Horses, mules, and asses are also subject to goitrous thyroid tumours. 

Malignant tumours occur in mules and asses ; but I have found very 
few cases of this kind on record. 

An instance of round and spindle-celled sarcoma of the lower lip of 
a mule, following injury by the bit, has been reported by Birchmore ; and 
these animals, as well as asses, are liable to melanosis. 

In the ass, cases of sarcoma of the colon, testis, and of the lung 
(chondro-sarcoma) have also been published. 

Pseudo-plasms consequent on actinomycosis, aspergillosis, bothryo- 
mycosis, and other parasitic affections, are of not uncommon occurrence 
in horses ; and Hutchinson 9 has described an example of intra-ocular 
hydatid cyst. Tuberculosis occurs, but it is not common. Tumour-like 
swellings in the walls of the stomach, due to oestrus larva, have also been 
noted. A tumour-like lesion of the lung, due to blastomycetic infection, 
has been reported by Frothingham ; 10 a mycotic maxillary tumour by 
Foulerton,u and a fibroid tumour-like mass of the spermatic cord, due to 
bothryomycosis, by Wolstenholme. 12 

1 Transactions of the Obstetric Society, London, 1890, vol. xxxi. 

2 Vide Journ. of Comp. Path., etc., 1903, vol. xvi., p. 127 ; ibid., 1905; April, p. 210; 
and Transactions of the Pathological Society, London, 1906. 

3 Bee. de lied. Vet., t. viii., p. 342. 

4 Transactions of the Pathological Society, London, 1890, vol. xli., p. 397. 

5 Univ. Pennsylvania Med. Butt., U.S., October, 1904. p. 265. 

6 British Medical Journal, 1882, vol. ii., p. 896. 

7 Journ. of Comp. Path., etc., 1902, vol. xv., p. 162. 

8 Rec. de MM. Vet.. June 30, 1902. 

9 Transactions of the Pathological Society, London, 1857, vol. viii., p. 413. 

10 Journal of Medical Research, Boston. U.S.. 1902, vol. viii., p. 31. 

11 Transactions of the Pathological Society. London, 1900, vol. li., p. 51. 

12 British Medical Journal, 1902, vol. i., p. 84. 



104 THE NATURAL HISTORY OF CANCER 



Ox. 

In bovine animals, according to Sticker, malignant tumours are very 
uncommon ; for of 5,795, only 7 were thus affected. 

The same authority states that their commonest seat is the uterus 
(16 in 74 cases) ; but I find that the liver 1 and stomach head the lists of 
most pathologists. Other parts liable to be affected are : the kidney, 
bladder, ovary, lung, eye, skin, vulva, penis, vagina, adrenal etc. all 
the chief varieties of malignant disease being represented. 

In the Chicago stockyards, Jobson and Loeb 2 found that cancer of 
the ocular conjunctiva was the commonest form ; and cancer of the vulva 
was also met with. 

There is a specimen of cancer of the rectum in the Hunterian Museum 
(No. 1,265, Pathological Series) ; and also of melanoma of a white cow's 
udder (No. 469, Pathological Series). 

Cadeac 3 has met with melanotic fibroma of the buttock of a cow 
seven years old, and he refers to other cases of the kind ; the Hunterian 
Museum contains a melanotic tumour, the size of a man's fist, which was 
removed from near the knee of a young cow ; and Bashford 4 has seen 
cases of melanotic sarcoma of the perineum and thigh of young cows. 

Hamburger 5 has described " chondro-fibro-melano-sarcoma " of the 
pleura and diaphragm of a cow; and Pike 6 " alveolar sarcoma " of the 
submaxillary region of a young bullock. 

Examples of " spina ventosa" of the superior and inferior maxilla, 
of the metacarpal and pastern bones, etc., are to be found in veterinary 
museums. 

Exostoses and osteomas are as common in bovine animals as in 
horses ; in the Hunterian Museum (No. 3,216, Pathological Series) is a 
large ivory ex ostosis from the frontal bone of an ox, which weighs 16 pounds, 
and measures 8 inches in diameter. Odontomata also occur. 

On examining the body of an apparently healthy cow, Colin 7 found 
the nerves studded with innumerable tumours (neuro-fibromata) , mostly 
of small size ; but, in connexion with the solar plexus, there was a large 
tumour, which weighed 5 pounds : other cases of this kind are referred 
to by Virchow. 

" Fibroid " tumours of the uterus, vagina, and submucosa of the 
stomach occur ; and in the Hunterian Museum (No. 194, Pathological 
Series) is an encapsuled bilobed tumour, of fatty appearance, attached 
by a long pedicle to the intestine of an ox. 

Cutaneous horns are sometimes met with ; in the Hunterian Museum 
there is a specimen of a large growth of this kind from the skin of the 

1 For note as to the frequency of " adeno-carcinoma " of the liver in Irish cows, vide 
Trotter (Journ. of Comp. Path., 1904, vol. xvii., p. 127). May not many of these 
tumours be due to some as yet undiscriminated microbic infection ? This is suggested 
by the undue incidence of the disease in the liver. 

2 Arch. f. klin. Chir., Bd. Ixx., 1903, p. 845 ; also Medicine, April, 1900. 

3 Bee. de Med. Vet., March 15, 1885. 

4 Scientific Report of the Cancer Research Fund, No. 2, 1905. 

5 Arch. f. path. Anat., Bd. cxvii., p. 427. 

6 British Medical Journal, 1896, vol. i., p. 989. 

7 Bee. de Med. Vet., t. viii., p. 947. 



CANCER AND OTHER TUMOURS IN ANIMALS 105 

forehead of an ox : similar formations have been seen on the neck and 
elsewhere. 

Ebinger 1 has recorded an instance of lipoma, found within the spinal 
canal of a cow. 

Papillary growths of the penis, vagina, 2 gall-bladder, 3 tongue, osso- 
phagus, etc., have been met with. 

Mammary adenomata and fibromata are fairly common. 

Multiple polypi of the mucosa of the small intestine of a cow have 
been reported by MacFadyean. 4 

Ovarian cystoma are not very exceptional, often attaining great size ; 
an example of multiple myomata of the uterus has been described by 
Spreull, 5 in which there were fifteen large tumours each about the size 
of a melon and many small ones. 

Cysts of abdominal, renal, intestinal, vaginal, and vesical location 
have also been reported ; and hydatids are common. 

Specimens of dermoid cysts containing hairs, teeth, etc., are to be 
found in the Hunterian and other museums ; and Windle 6 has met with 
a teratoma of the sphenoid in a calf. 

In the Hunterian Museum (No. 161, Pathological Series) is a dermoid 
cyst from the shoulder of a cow with six legs ; the cyst contained hairs, 
fatty, and calcareous matter. An instance of a branchial dermoid cyst 
of the lower part of the neck by Trotter,? is also on record. 

Bovine animals are specially prone to tubercle, as well as to the w' 
same kinds of pseudo-plasms as horses. 

Pig. 

There is a consensus of opinion among veterinarians, which finds 
some support in the paucity of recorded cases, that malignant tumours 
are of rare occurrence in swine. Of over 100 malignant tumours examined 
by MacFadyean, Cadiot, and Roger, there was not a single example from 
a pig ; and Sticker's list of 1,170 similar tumours comprises only 12 from 
this animal. Gaylord and Zink 8 found 4 malignant tumours among 
about 2,000 swine, mostly young, slaughtered at Buffalo. Judging by 
recorded cases, the kidney, skin, and liver are the commonest seats of 
initial manifestation. Other localities noted are intra- abdominal, lymph- 
glands, submaxillary gland, parotid, testis, penis, maxillary bones, 
vertebrae etc. 

Hamburger 9 has made detailed study of a case of kidney sarcoma ; 
and Bashford has met with mixed-celled sarcoma of the submaxillary 
gland. Several cases of Hodgkin's disease in swine have also been 
reported. 

1 Veterinary Journal, 1902, p. 170. 

2 For report of a large condylomatous tumour of the vagina of a young cow. vide 
Waghorn, Veterinary Journal, May, 1905, p. 253. 

3 Virchow has described and figured a case (" Path, des Tumeurs," t. i., 1867, p. 337). 

4 Journ. of Comp. Path., etc., 1902, vol. xv., p. 155. 

5 Journ. of Comp. Anat., etc., 1904, vol. xvii., p. 64. 

6 Journ. of Anatomy, vol. xxii., p. 420. 

7 Journ. of Comp. Path., etc., 1903, vol. xvi., p. 55. 

8 Clinical Journal, June 11, 1902, p. 125. 

9 Arch. f. path. Anat., Bd. cxvii., S. 422. 



106 THE NATURAL HISTORY OF CAXCER 

Published records of non-malignant tumours in swine are even more 
scanty, than those concerning malignant tumours. "Fibroids" have 
been discriminated in the uterus and vagina, and in the latter organ 
Wolffian duct cysts occasionally occur. Papillomatous tumours of the 
intestine, exostosis of the ischium, bothryomycetic pseudo-plasms, 
hydatid cysts of the liver, etc., and goitrous tumours of the thyroid, have 
also been noted. 

Swine are but moderately prone to tubercle. ^ 

Sheep. 

Sheep are unquestionably much less prone to malignant tumours 
than any of our common domesticated animals ; indeed, Sticker's list 
of 1,170 of these tumours, comprises only 7 from sheep : of 6,800 sheep 
slaughtered during four years at Hah' fax, only one instance of malignant 
tumour was found. 1 

Of the few recorded cases, in the great majority the liver was the site 
of initial manifestation ; other parts affected being the maxillary bones, 
eye, orbit, lung etc. 

Examples of intra-ocular and orbital malignant tumours have been 
described by Axe and others ; and a specimen of this kind is in Guy's 
Hospital Museum. 

An example of " spina ventosa " of the inferior maxilla, owing to the 
growth of central sarcoma, is preserved in the Edinburgh Anatomical 
and Pathological Museum (No. 6 : 487) ; and the Cancer Research Staff has 
lately examined a specimen of ossifying sarcoma of the same bone. 

Sharp 2 has published an account of a large cystic myxoma attached 
to the colon. 

With regard to non-malignant tumours, very few modern instances 
have been recorded. Ovarian cystomata occur, a specimen weighing 
7 pounds having been met with. Poly cystic disease of the kidneys has 
also been recognized, and there is a specimen of this kind in the Hun- 
terian Museum. In this connexion, it is of interest to note the occur- 
rence of polycystic disease, affecting concomitantly several internal organs 
as well as the kidneys e.g., liver, lungs, and even the cardiac musculature, 
of which Cruveilhier has reported examples. Eve 3 has seen a cyst, con- 
nected with the undescended testis of a sheep with hermaphroditic mal- 
formation. Fatty tumours are stated to be met with in sheep, but I 
cannot cite a modern instance, unless the curious case described by 
Paget, 4 be so regarded. Here a mass of fatty outgrowths surrounded 
the outside of the heart, and processes were embedded in its substance, 
some of which even projected into its cavities. 

Papillary growths and cutaneous horny excrescences are met with : 
some remarkable examples of the latter have been recorded, e.g., a horn 
connected with the throat, weighing 26 pounds, and a similar formation 
of the flank 3 feet in length. 

1 JY F. Hodgkinson. Journ. of Gotnp. Path., etc., 1903, vol. xvi., p. 269 ; a case of 
cystic cancer of the liver. 2 Journal of Anatomy, 1896, vol. xxx., p. 559. 

3 Transactions of the Pathological Society, London, 1889, vol. xl., p. 463. 
" Surgical Pathology," 1853, vol. ii., p. 93. 



CANCER AND OTHER TUMOURS IN ANIMALS 107 

Many instances of dermoid cysts are preserved in museums. A 
piliferous formation of this kind, replacing one of the kidneys, of which 
there was no trace, is in the Hunterian Museum ; it contained masses 
of rolled-up wool, oily and fatty matters (No. 1,904, Pathological Series) : 
another specimen, in the Hunterian Museum at Glasgow, 1 is described 
as : " cyst from a sheep's leg ; a long spindle-shaped cyst, with fairly 
thick walls, covered internally with fine hairs ; it is filled with balls of 
tightly compressed hairs, which had grown from its surface, shed, and 
accumulated gradually." Other examples of these formations are con- 
tained in the London Hunterian Museum ; and two tumours of this kind, 
derived from a single animal, are there preserved (Nos. 159 and 160, 
Pathological Series). 

In the teratological series of the same museum (No. 373) is a pre- 
paration showing a lock of wool, growing from a dermoid patch on the 
ocular conjunctiva. 

Here also may be mentioned the occurrence of aberrant teeth in cysts 
and fistulse of the neck, between the angle of jaw and external auditory 
meatus ; which seem to arise from defective closure of a branchial cleft, 
with indications of a tendency to the formation of a redundant rudi- 
mentary mouth. An example of a dentigerous cyst of the upper jaw 
of a young sheep, associated with a malformed central incisor, may be^ 
seen in St. Bartholomew's Hospital Museum (1 : 119a). 

Among the pseudo-plasms of sheep, reference must be made to coccidial 
tumours, such as those described by Nocard 2 in the intestine. 

Tubercle occurs in sheep, and even in goats ; and not so very rarely. 

Goat. 

Eggeling 3 has reported a case of mammary cancer in a female goat 
(Capra hircus). 

A curious form of quasi-malignant tumour of the anus of female 
Angora goats imported from South Africa, has been described by De 
Korte ; 4 which strikingly illustrates the difficulty of discriminating certain 
tumours in animals from mycotic pseudo-plasms ; for, while the author 
regards this malady as a true malignant tumour, other pathologists 
describe it as a granuloma. 

Goats are certainly very rarely attacked by malignant disease ;X 
indeed, the above are the only modern examples of the kind known to 
me. Large odontoniata, in connexion with the jaws, have been met with ; 
and these have sometimes been described as sarcomatous. Cutaneous 
horns, and hydatid cysts, also occur in goats. 

Deer. 

V Deer seem to be as little liable to malignant tumours as goats. Otto 
refers to melanosis in a stag, but I cannot cite a single modern instance. 
In the museums, one finds specimens of fibroma of the antler, piliferous 

1 "Catalogue of Hunterian Museum, Glasgow," 1900, p. 393. 

2 Journal of Pathology, etc., 1893, vol. i., p. 404. 

3 Cited by Sticker, Arch. f. klin. Chir., 1902, Bd. Ixv., p. 661. 
* Transactions of the Pathological Society, London, 1905. 



108 THE NATURAL HISTORY OF CANCER 

dennoid of the conjunctiva, exostosis of the skull, ossiform tumour from 
the brain, bony deposits in the omentum, hydatid cysts etc. 



Rabbit. 

Malignant tumours are certainly of extremely rare occurrence in these 
animals ; indeed, hardly any really reliable case records exist. Per 
contra , rabbits are so exceedingly subject to psorospermosis, with its 
attendant tumour-like lesions, that in tame animals this malady may 
be said to be universal. 

A few years ago Lack * claimed to have succeeded in experimentally 
producing cancer in a rabbit, the uterus being one of the structures 
implicated. 

Lack's experiment has since been repeated by many pathologists, but 
no one has succeeded in reproducing similar morbid appearances. 

Shattock, 2 having had occasion to examine the body of a rabbit that 
had been killed as obviously diseased, found a curious tumour-like, cystic, 
villous new formation, having the general aspect of a " chorionic mole," 
invading both uteri. Histological examination revealed the structure of 
papilliferous columnar-celled epithelioma. Similar formations were found 
in the peritoneum. The author regards this tumour as an example of 
spontaneous uterine cancer ; and suggests that, in Lack's case, the disease 
probably had similar origin. 

In the absence of special examination directed to the exclusion of 
psorosperms, it seems undesirable to accept these cases, as being scien- 
tifically verified examples of uterine cancer in the rabbit ; and further 
observations are needed to establish the occurrence of this condition in 
these animals. 

The Museum of the Royal College of Surgeons of Ireland contains a 
specimen 3 of " fungus hsematodes " of the dorsal surface of the scapula 
of a rabbit a firm, elastic, nodular tumour, larger than a goose's egg, 
being displayed. 

Rabbits are also liable to melanosis. Lubarsch 4 has lately described 
a large renal tumour in a rabbit. 



Mouse. 

Until the many various parasitic pseudo-plasms, to which mice and 
rats are specially prone, have been more thoroughly studied and dis- 
criminated, it will be impossible to form a reliable conclusion as to 
the incidence of true tumours in these animals. 

Independently of the so-called " Jensen's tumour " and its variants, 
the nature of which will be discussed in a subsequent chapter, 5 several 
instances of malignant tumours in mice have been reported. 

* Journal of Pathology, 1900, vol. vi., p. 154. 

- Transactions of the Pathological Society, London, 1900, vol. li., p. 56. 

4 Cent. SI. '/. attg. Path., etc., 1903, vol. xvi., p. 9. 
6 Chapter VTII. 



CANCER AND OTHER TUMOURS IN ANIMALS 109 

Even as far back as half a century, Crisp * exhibited at the London 
Pathological Society a malignant tumour of the pectoral muscle of a 
wild mouse, caught in a trap. 

According to the Cancer Research pathologists, 11 cases of malignant 
disease were met with in 27,000 mice examined ; and they seem to be of 
more frequent occurrence in tame than in wild varieties. 

Tumours of this kind have been met with in the mammary region, 
skin, jaw, intestine, lung, vulva etc. Mice are also subject to melanosis. 
Haaland has described chondro-sarcoma ; and Ehrlich chondroma. 

Tyzzer 2 has reported instances of two independent growths in the\ 7 
same mouse e.g., cylindrical epithelioma of the lung, concomitant with 
adenoma of the kidney etc., and other examples of so-called " sponta- 
neous " tumours. 

With regard to the non-malignant tumours of mice, the published 
records known to me are exceedingly scanty : Spencer 3 has described 
an instance of " hornifying excrescence " of the head of a wild mouse ; 
Treves 4 a similar formation on the neck ; and other examples of this kind 
may be found in the museums. Various forms of adenoma and cyst- 
adenoma have also been reported. 

Quasi-malignant growths due to parasitic sporozoa, blastomycetes, 
bacteria, pseudo- tuberculosis, nematodes etc., often occur ; 6 and some- 
times these pseudo-plasms also mimic non-malignant tumours. 

According to Lydia Rabinowitsch, mice and rats are prone to tubercle, 
infected animals readily conveying the disease to others of their species. 



Rat. 

As might be expected a priori, there is great similarity with regard 
to neoplastic proclivity, between rats and mice. 

Malignant epithelial and connective-tissue tumours, do undoubtedly 
occur in rats, but they are very rare. 

A good example of ossifying sarcoma of the leg bones of a rat, has 
been described and figured by Bland-Sutton ; 5 and these animals are also 
liable to melanosis. 

The epidemic occurrence of so-called " cancer " in rats, as well as a 
contagious form of the malady transmissible from one animal to another 
by implantation, as in the case of mice, have also been reported by 
several pathologists e.g., Hanau, Eiselsberg, Loeb, Velich, etc. The 
claim of these pseudo-plasms to be regarded as true malignant tumours 
has yet to be substantiated ; all the indications at present available 
seem to me to point rather to their affinity with the granulomata and 
" infective epithelioses," to which rats are as prone as mice. 

Here mention may be made of the fact that tumours of this kind 

1 Transactions of the Pathological Society, London, 1854, p. 348. 

2 Journal of the American Medical Association, October 20, 1906, p. 1237 ; Fourth 
Rep. Croft Cancer Commission, Boston, U.S., 1907, p' 27. 

3 Transactions of the Pathological Society, London, 1890, vol. xli., p. 402. 

4 Transactions of the Pathological Society, London, 1888, vol. xxxix., p. 463. 

5 Journal of Anatomy, vol. xix., p. 456. 

6 For instances experimentally produced, vide Chapter X. 



110 THE NATURAL HISTORY OF CANCER 

have been produced in rats, by inoculating them with certain pathogenic 
yeasts (Busse, Curtis, Sanfelice, Wlaeff etc.). 

Non-malignant tumours seem to be almost as uncommon in rats as 
in mice. An example of subcutaneous fibroma of large size, has lately 
been reported by Lecene and Esmonet ; l and in a pied rat, Bland-Sutton 2 
met with a similar tumour in the neck ; Shattock 3 has described adeno- 
fibroma of the mamma of a male pied rat ; Loeb 4 adenoma of the mamma 
of a female rat ; and Bland-Sutton ovarian hydrocele. 

Other Mammalian Animals. 

An interesting instance of columnar-celled epithelioma of the ileum 
in a lion has been described by Harrison : 5 this animal was born in the 
Clifton Zoo, and passed the sixteen and a half years of his life in a com- 
paratively small cage there, his general health having been good. He 
died after a lingering illness, marked by progressive wasting. Post- 
mortem examination revealed a circular cancerous growth, constricting 
the lumen of the bowel, just above the ileo-csecal valve, which on micro- 
scopical examination had the structure above mentioned. 

An example of cancer, in an aged lioness, has been reported by Welsh, 
of Sydney, New South Wales, who has also met with an instance of the 
same disease in an old tigress. 

Cystic tumours of the liver, and exostoses of the vertebrae and other 
bones, have also been noted in lions ; as well as rounded bodies, like 
detached fibromyoma, loose in the peritoneal cavity. 

In the Glasgow Hunterian Museum, 6 is a portion of a leopard's stomach, 
with a necrotic fibroid tumour projecting beneath the mucosa ; and 
Bland-Sutton has met with cystic disease of the ovaries in a tigress. 

Many years ago, E. Rousseau reported that malignant tumours were 
"' not infrequent," among the white bears confined in the Jardin des 
Plantes at Paris. 

An instance of cancer of the stomach of a rhinoceros has lately been 
cited by Renshaw. 

A large spongy exostosis, invading the superior maxilla and adjacent 
bones of the skull of a hippopotamus, has been seen by Otto ; and, by the 
same pathologist, odontoma of the elephant's tusk. 

Thick-walled cysts of the liver of the porpoise and camel, sometimes 
calcified, are preserved in museums. 

A cancellous bony outgrowth from the inferior maxilla of the Vir- 
ginian opossum is in the Hunterian Museum ; which also comprises two 
subcutaneous dermoid cysts, with steatomatous laminated contents, one 
from the back and the other from the abdominal region of the same 
animal. 

Multiple myomata of the uterus of a kind of beaver (Myopotamus 
coypus), have been described by Hilgendorf and Paulicki. 

1 Bull, et mem. Soc. Anat., Paris, 1905, vol. Ixxx., p. 38. 

2 Op. cit. 

3 Transactions of the Pathological Society, London, 1893, vol. xliv., p. 229. 
* Journal of Medical Research, 1902, vol. viii., p. 46. 

5 Op. cit. 

6 Anatomical and pathological collection (34 : 15). 



CANCER AND OTHER TUMOURS IN ANIMALS 111 

Whales are subject to warty outgrowths of the skin, which are often 
due to parasitic cirripedia ; as described by Weltner. 

A malignant renal tumour (derived from an adrenal " rest "), has 
been described by Bland-Sutton in a marmot ; the same author has also 
met with odontoma in this kind of animal ; and Otto has seen " spina 
ventosa " of the inferior maxilla. 

Even in marsupial animals, a feAv instances of malignant and other 
tumours, have been reported. 

In the Hunterian Museum (No. 1,038, Pathological Series) in one half 
of the inferior maxilla of a kangaroo, distended by a large central ossifying 
sarcoma ; and, according to Otto, specimens of " spina ventosa " and 
exostoses, in marsupial animals, may often be seen in museums. 

Examples of in tr a- abdominal lympho-sarcoma in dasyures, have been 
described by Eve and Bland-Sutton ; while, the latter author, has also seen 
cancer of the marsupial pouch of a short-headed phalanger. 



Birds. 

It is stated by Pick and Poll, that malignant tumours are of very 
rare occurrence in birds ; but, if this is meant to apply to the common 
domesticated kinds, it cannot be accepted as quite accurate ; for, as 
Heusinger long ago pointed out, malignant tumours are not so very 
uncommon in these, and this is quite in accord with modern indications. 

The common domestic hen seems to be remarkably prone to sarcoma, 
instances having been reported by Hathaway, Patterson, Birchmore, 
Crisp, Parker etc. ; melanosis also occurs. Squamous-celled epithelioma 
of the floor of the mouth has been described by Pick ; an enormous quasi- 
malignant ovarian tumour by Bland-Sutton ; and two instances of 
epithelioma of the small intestine by Ehrenreich and Michaelis. 

A large fibre-cartilaginous tumour, from the subcutaneous tissue of 
the thigh of a domestic fowl, is to be found in the Museum of the Royal 
College of Surgeons of Ireland ; and a large fatty tumour was removed from 
the pectoral region of a hen by Crisp. Ehrenreich and Michaelis have 
described two examples of fibroma of the mesentery. Exostoses, hyper- 
ostoses, and ossified tendons, are not particularly rare ; while sebaceous 
cysts, hornifying outgrowths, warts, and even corns, are fairly common. 

Large cystomata of the hen's ovary are often met with, as the 
specimens in many museums testify. 

Mougie has seen a large serous cyst of the abdomen of a hen ; and 
dermoid cysts, containing feathers, also occur. 

A quasi-sarcomatous tumour from the lung of a Bernicle goose is 
preserved in Guy's Hospital Museum (No. 1,793, Pathological Series). In 
the Museum of the Irish College of Surgeons (D. f., 56), is an immense 
" fibroid " tumour, " as big as a large melon," which occupied nearly all 
of the greatly distended abdominal cavity of a goose ; this tumour was 
so slightly attached that, when the abdomen was opened, it fell out, so 
that its exact point of attachment could not be determined, but it was 
surmised to have originated from the oviduct or intestine. Harrison 1 
1 Bristol Med.-Chir. Journ., 1894, vol. xii., p. 288. 



112 THE NATURAL HISTORY OF CANCER 

met with a similar tumour, which weighed at least one pound, in an ancient 
goose supposed to be over thirty years old, which died in the Clifton 
Zoo ; and in this instance the pedicle of the tumour was connected with 
the mesentery. A large, lobulated, quasi-fibrous tumour, from the neck 
of a goose, is in the Hunterian Museum (No. 307, Pathological Series). 
Dermoid cysts, containing feathers, have also been found in these birds. 

Other examples of tumours in birds of which I have cognizance are : 
A subcutaneous round-celled sarcoma, of yellow colour, of the wing of a 
dove (Woods Hutchinson) ; alveolar sarcoma of the pectoral region of a 
golden plover, in the Hunterian Museum ; malignant tumour of the 
pectoral region of a canary (Crisp) ; " fungoid " tumour of the eye of a 
canary (Crisp); " spina ventosa" of the great wing-bone of a parrot, 
cited by Otto ; myxo-sarcoma of the pectoral muscles of an Indian 
parakeet (Bashford) ; malignant tumours among the carnivorous birds 
of the Paris Jardin des Plantes, noted by Rousseau ; ovarian tumour in a 
pheasant, by Slater ; large sebaceous cyst of the pectoral region of a 
pigeon, in the Irish College of Surgeons' Museum ; I had a thrush which 
developed a similar cyst on the head, whence sprang a horn-like out- 
growth ; and formations of this kind have been seen in other birds (dove, 
canary, partridge) ; fibroma of the thigh of a grouse in the Hunterian 
Museum ; the oldest inhabitant of the Clifton Zoo, a griffin vulture, was 
subject to an exostosis of the foot, as reported by Harrison ; turkeys seem 
to have special proclivity to large ivory exostoses of the bones, of which 
there are specimens in the Hunterian and other museums, to which 
J. Hutchinson * has specially called attention ; on each metatarsal bone 
of a young rhea Bland-Sutton found an enchondromatous tumour ; 
among the Hunterian preparations in the English College of Surgeons' 
Museum, is : "A tumour from the belly of an ostrich " of fibre-cellular 
structure ; also an exostosis on a cervical vertebra of the same bird ; and 
a cyst developed from an unobliterated vitello-intestinal duct, attached 
to the intestine of an emu. 

Contagious tumour-like lesions due to tubercle, psorospermosis and 
other parasitic infections are common in birds. To this list the con- 
tagious inoculable malady called Molluscum contagiosum, especially prone 
to occur in fowls and pigeons, must be added ; and its similarity with the 
like-named malady of human pathology is also noteworthy. 

Birds are as a class very prone to tubercle, especially the common 
domesticated kinds. 

Reptiles and Amphibians. 

With regard to these groups of animals all that can be said is, that 
malignant and benign tumours are known to occur among some of their 
members. By systematic post-mortem examination of the bodies of 
salamanders from the Berlin Biological Institute, Pick and Poll 2 have 
demonstrated cystic glandular cancer of the testis of the giant sala- 
mander (Crypto-branchus japonicus). These pathologists have also found 
a benign tumour, which they regard as thyroid adenoma, growing from 

1 Archives of Surgery, 1893, vol. iv., p. 121. 

2 Berlin, klin. Woch., 1903, No. 23, S. 518 ; No. 24, S. 546 ; and No. 25, S. 572. 



CANCER AND OTHER TUMOURS IN ANIMALS 113 

the neck of the snake-necked tortoise ; and also a tumour, as to the nature 
of which they are doubtful, growing from the left side of the neck of a 
Salamandra maculata. Plehn 1 has collected records of other cases of 
tumours in salamanders, lizards, and frogs. 

A specimen of columnar-celled cancer of the kidney of a frog (Small- 
woods), has been verified by the Cancer Research Staff. 

An interesting example of cancer of the ovaries with widespread 
dissemination, in a python, that had lived for fifteen years in the London 
Zoo, where it died cachectic on account of this ailment, has been described 
by Bland-Sutton ; 2 and this author has also met with multiple chondro- 
mata, in a rachitic Indian lizard, from the same collection of animals. 

Sarcoma in a frog has been reported by Murray ; and Gebhardt has 
investigated two pyloric tumours in frogs, due to protozoa. 

Otto has seen " spina ventosa " of the caudal vertebrae of a chameleon ; 
and there is a specimen showing exostoses on the ribs of a chameleon, in 
the Hunterian Museum (No. 797). 

Sandifort has met with exostoses on two vertebrae of a boa-constrictor. 

Fish. 

We have to note the great proclivity of fishes to parasitic infections 
of various kinds (sporozoa, mycoses, bacteria, nematodes etc.), many 
of which cause large swellings, which resemble malignant tumours. 3 
Epidemics among river fishes (barbel, pike etc.), due to parasitic myxo- 
sporidia, have been noted in Germany ; and this form of disease is common 
in the pike's bladder. 

From a crowd of parasitic pseudo-plasms, the Cancer Research Staff 
claim to have demonstrated sixteen examples of true malignant tumours 
in fishes, some of them pelagic ; but, long before this body took the 
matter up, instances of malignant tumours in fish had been reported, 
especially in carp, by Crisp, Bland-Sutton, Sibley, Ohlmacher, and others. 

Carp have been kept, under artificial conditions, from the remotest 
times ; and, it is not without significance, that just this fish should have 
furnished so many examples of malignant tumours. 

A sarcomatous tumour from a golden carp, has been described and 
figured by Bland-Sutton, 4 from a specimen in the Hunterian Museum ; a 
similar tumour of much larger size, also in a carp, had previously been 
described by Crisp ; 5 examples of malignant epithelial tumours in carp 
have been reported by Battaillon, 6 and Bashford. 7 Sibley, 8 having 
examined a specimen labelled " multiple sarcoma of a carp " from a 
German pathological museum, found that the tumours consisted almost 
entirely of psorospermia. 

1 Zeitschr. f. Krebsforschung, 1907. 

2 Journal of Anatomy, vol. xix., p. 464. 

3 For some interesting remarks on this subject, vide Gurley and Tyzzer, " Tumours 
and Sporozoa in Fishes," First Annual Report of the Cancer Committee, Harvard 
Medical School, Boston, U.S., October, 1900, etc. 

* Journal of Anatomy, vol. xix., p. 447. 

6 Transactions of the Pathological Society, London, vol. v., p. 347. 

6 Zeite. f. Fleisch. u. Mikh.-Hyg., 1898, S. 151. 

7 Scientific Reports of the Cancer Research Fund, 1905, No. 2. 

8 Transactions of the Pathological Society, London, 1890, vol. xli., p. 322. 

8 



114 THE NATURAL HISTORY OF CANCER 

Lately, several instances of " cancer epidemics " in trout, have been 
reported by Pick, Scott, Gilruth, Bashford etc. ; and, in all these cases, the 
fish had been long kept under artificial conditions in special " hatcheries." 

Two examples of malignant tumours from fish (cod, gurnard), which 
had lived under natural conditions, have also been studied by the Cancer 
Research Staff i 1 and Ohlmacher has seen sarcoma of the peri- vertebral 
connective tissue, with metastases, in a lake pike. 

Curious tumours due to sporozoa, in a minnow (Cyprinus phoxinus), 
have been described by Davaine ; and, in a stickleback (Gasterosteus 
trachurus), by L. Tait ; while, in the Hunterian Museum, is a dace 
(Cyprinus lenciscus), the surface of whose body is covered by " a 
mycoderm confervoid growth " (No. 2,305). 

A striking feature in the neoplastic pathology of fishes, is the great 
frequency of exostoses and bony tumours, w r hich are generally multiple. 

In the chief pathological museums, many specimens illustrating the 
proneness of codfish to multiple exostoses and bony tumours are to be 
found ; 2 their seats of election are the vertebrae, superior maxilla, tail 
etc. In the stomach of these fish, submucosal " fibroid " has been met 
with ; and a similar tumour has been found in the subcutaneous connective 
tissue. Specimens of the sclerotic of the eye of a codfish, exhibiting 
numerous white nodules, due to parasitic gregarinse, are preserved in the 
Glasgow Hunterian Museum (39 : 32). As previously mentioned, spindle- 
celled sarcoma of the air-bladder of a codfish, has been investigated by 
the Cancer Research Staff ; also intra-abdominal glandular cancer in a 
gurnard. 

Multiple bony tumours of the skeleton of some chaetodons are of such 
common occurrence that W. Bell, who first specially called attention to 
them, rather rashly concluded that they were " natural " in this fish. 

Large bony tumours of the occipital region of the skull etc. are also 
often met with in Ephippus gigas and faber, as reported by Valenciennes. 

Otto long ago called attention to the frequency of large exostoses, 
connected with the spines of the vertebrae of scabbard fish (Lepidopus 
peronii etc.), and of the spiny fish (Sparus erythrinus) ; Gervais has since 
confirmed and extended these observations, describing a large bony 
outgrowth from the occipital crest of Pagrus unicolor. 

Exostosis of the jaw-bone of a pike has also been described. 

The Anatomical and Pathological Museum of the College of Surgeons 
of Edinburgh (5 : 1726), contains a specimen showing extreme hyper- 
ostosis of many caudal vertebrae, from a haddock ; and, in the Glasgow 
Hunterian Museum, a portion of one of these fishes is exhibited, so as to 
display the innumerable colonies of psorospermia parasitic in its flesh 
(39 : 33). 

1 Scientific Reports, No. 1, 1904, p. 7. 

2 Glasgow Hunterian Museum, Nos. 5, 172, and 172a ; and in the London Hunterian 
Museum, Nos. 796 and 1,039. 



CHAPTER VI 
TUMOURS IN VEGETABLE ORGANISMS 

IN this chapter I propose to show: (1) that tumours, analogous to the 
malignant and non-malignant tumours of human and animal pathology, 
occur also in vegetable organisms ; (2) that such tumours are dervied from 
abnormally evolving buds ; and (3) that in the vegetable world tumour- 
like formations are of very common occurrence, as the consequence of 
parasitic and other irritants ab extra. 

Bud Formation and its Anomalies. 

The process of gemmation in plants is of great importance, for the 
understanding of their development and organization ; and it is capable 
of throwing much light on the analogous processes in animal and human 
ontogeny, to which biologists and pathologists have hitherto paid far too 
little attention for gemmation has its pathological as well as its physio- 
logical outlets. The simplest buds consist either of single undiffer- 
entiated cells, or of groups of such cells derived from single cells, the 
differentiated tissues of the parent plant having no share in the formation 
of the primitive bud, and no connexion with it until a later period. 

Usually buds develop in organic connexion with the parent stock ; 
but sometimes, as in the tiger-lily, they fall off and develop separately 
(bulbils). The branch-bud here acts like a seed-bud, but is capable of 
developing without fertilization. Hence buds artificially separated, may 
be used for purposes of propagation, as in the familiar processes of 
grafting, budding, layering, etc. Thus, each bud is potentially a new 
individual having, under favourable circumstances, the power of evolving 
into a perfect organism. 

But the degree of development actually attained, usually falls far short 
of this ; for, owing to disturbances in nutrition, buds may be variously 
modified in adaptation to other ends. Thus, in extreme cases, they may 
remain permanently undeveloped ; or they may remain for long periods, 
even for years, in a dormant or latent state ; and yet, under favourable 
conditions, their activity may revive. 

When their development is somewhat less restricted, the products may 
be dwarfed, or evolved into spines, tendrils, twigs, or various irregular 
formations, which may properly be called tumours. 

In the higher vegetable organisms buds are usually distributed with 
great regularity, being either terminal or axillary ; buds arising in any 
other way, are said to be of adventitious origin. 

115 82 



116 THE NATURAL HISTORY OF CANCER 

Now, adventitious buds differ from normal buds only in respect to 
position ; for, they originate otherwise in precisely the same way, as those 
normally formed on the axis. Adventitious buds have been found on 
almost every part of plants. They sometimes develop in extraordinary 
numbers on the stems and branches of trees, owing to some interference 
with the vegetation of the normal buds ; and they may be evoked by 
wounds. When a begonia leaf is placed in damp soil, and incisions are 
made across its " nerves," buds spring from every incision ; and as many 
fresh plants may be obtained in this way as the leaf has received wounds. 
The Dutch bulb growers have cleverly availed themselves of a similar 
property, to propagate hyacinths ; this they effect either by making two 
or three deep incisions into the base of the bulb destroying the nascent 
flower-stalk when, after a short time, numerous small buds form along 
the edges of the cut surface ; or, by scooping out the interior of the base 
of the bulb, and so leaving exposed the cut ends of the sheathing leaves, 
from which buds soon spring in great numbers. 

Leaves subjected to slight pressure, and in process of decay, frequently 
develop buds in a similar way. 

Degrees of injury which fall far short of this, such as those produced 
by various mild irritants, as described by Waldenburg, cause local 
thickenings, owing to increased growth and proliferation of the cells of 
the part. 

In like manner, as will be seen in the sequel, the various kinds of galls 
arise. 

In a general way, the root is distinguished from the stem by the 
absence of buds ; but, under exceptional circumstances, adventitious buds 
may form even on roots. Duhamel, having planted a willow with its 
branches in the ground and its roots in the air, saw its roots become 
covered with leaf-bearing buds, while the buried branches produced roots. 
The production of a flower-bud has been noticed on the root of a species 
of Impatiens. In some cases, the divided root suffices for the reproduction 
of the entire plant, as in the Japan quince, the Osage orange, and 
especially the Paulownia the roots of which, even when cut into small 
pieces, can develop into perfect trees. 

There are many plants which produce buds on their leaves. This is 
of much commoner occurrence among the lower orders, and the ferns, 
than with the Phanerogamia. As examples among native plants may be 
instanced the watercress, Cardamine pratensis, and Malaxis paludosa 
in the last named, the buds are known to be derived from single cells of 
the surface of the leaves. Begonias exhibit this power in a remarkable 
degree ; in some instances, single scales from the leaves or stem habitually 
develop into young plants. One of the best-known instances is that 
afforded by Bryophyllum calycinum, a succulent tropical plant, whose 
leaves produce buds furnished with roots, stem, and leaves, at the ex- 
tremities of its lateral nerves. These buds, which fall off spontaneously 
and root in the earth, may be compared to ovules which do not need to 
be fertilized before developing ; and the leaf of the Bryophyllum may be 
regarded as an open carpel, in which the seeds have been developed by 
nutritive action alone. Consideration of the subject in this light, leads us 



TUMOURS IN VEGETABLE ORGANISMS 



117 



to regard the bud as an individual vital centre resembling the ovule. 
Many facts in vegetable physiology and pathology confirm this view. 
Schleiden regarded the ovule as a modified bud, and the now well-authenti- 
cated cases of parthenogenesis in plants support his theory. In these 
cases, new individuals are developed from unimpregnated ovules, as from 
buds, the defect in the ovular reproductive power, which ordinarily 
renders impregnation necessary, being removed. The ovule or seed-bud, 
then, differs from the branch-bud essentially only in this : that it generally 
needs for its development the fertilizing influence of the pollen. The 
fecundity of Bryophyllum, completes the analogy between the bud and the 
fertilized ovule. According to Hofmeister, the buds of Bryophyllum 
arise before the complete unfolding of the leaf, as small masses of un- 
differentiated parenchyma, in the deepest parts of the crenations of the 
leaves. 

Buds thus arising, may take root and give origin to leaf-bearing 
branches, while still in connexion with the parent plant, as in Drosera 




FIG. 1. AN ADVENTITIOUS LEAF-BEARING SHOOT DEVELOPED ON A LEAF OF 
EPISCIA BICOLOR (MASTERS). 

intermedia, Episcia bicolor etc. (Fig. 1), though they generally develop 
more readily after the leaves have fallen off. Adventitious buds have also 
been found on the petiole, lamina, stipule ; and, in short, on every part of 
the leaf. It thus seems as if buds may arise wherever undifferentiated 
cells, still capable of growth and development, are present. 

Such facts as the foregoing show, that there is no specific distinction 
between somatic and germ cells, as Weismann has maintained ; they 
indicate that the reproductive properties manifested by somatic and germ 
cells are the same in kind, and that they differ only in degree. In short, 
the whole history of gemmation in plants, testifies against fundamental 
difference between somatic and germ cells. 

It seems probable that the capacity of the higher vegetable organisms, 
for manifesting these anom'alous kinds of bud formation, may be due to 
reversion ; at any rate, they remind us of the proliferous outgrowths so 
common among the Thallophyta. 

The shoots which spring from buds usually develop into structures 
of the same form, as those which compose the parent plant ; but, it occasion- 



118 



THE NATURAL HISTORY OF CANCER 



ally happens, that particular buds develop differently from others of the 
same stock. ' Gardeners call these changes " sports " ; by Darwin they 
were described as ' ; bud variation " ; while De Vries discriminates all 
abrupt transformations of this kind as " mutations." The common 
moss-rose is considered by Darwin to have originated in this way from the 
Provence rose. 

Not only normal, but adventitious buds as well, are liable to this kind 
of mutation. Fronds of the same fern, for instance, often manifest 
striking morphological variations ; of this a remaikable example is figured 
below (Fig. 2), which represents a portion of a frond of Pteris quadriaurita 
bearing an adventitous bud, whence foliage very different from that 
of the rest of the plant has emerged. Mutations of this kind, are of 




FIG. 2. PORTION OF A FROND OF PTERIS QUADRIACRITA, IN WHICH THE FOLIAGE 
EMERGING FROM AN ADVENTITIOUS BUD IS VERY DIFFERENT FROM THAT OF THE 
BEST OF THE PLANT (MASTERS). , 

much commoner occurrence among the lower than among the higher 
orders of plants ; and among cultivated than among wild species. 

Many mutations were regarded by Darwin as due to reversion ; others 
he ascribed to the so-called " spontaneous variability," understanding 
by this term variation of which the causes were not obvious. 1 

In formulating the doctrine of natural selection, which is peculiarly 
his own, there can be no doubt that Darwin failed to attach due weight 
to the occurrence of mutations independently of selection and of adapta- 
tion. It has since been shown that numerous variations of this kind do 
occur, some of which are obviously disadvantageous to their modified 
possessors, while others are neither advantageous nor disadvantageous. 

It is with these mutations that the various pathological new formations 
should be classed. Here brief reference must be made to the conditions 

1 According to H. Spencer : " Spontaneous variations are interpretable as results of 
miscellaneously compounding the changes wrought in different lines of ancestors by 
different conditions of existence." 



TUMOURS IN VEGETABLE ORGANISMS 119 

which determine the incidence of gemmation, gamogenesis, and alterna- 
tion of generations ; and, it will suffice for our immediate purpose, if I state 
that the conclusion derived from the consideration of the ensemble of 
this important subject is, that the outcome of growth in any particular 
case is mainly determined by nutrition. Thus gemmation or asexual 
multiplication may be regarded as the outcome of favourable nutritive 
conditions, resulting in vegetative growth ; while gamogenesis is likely to 
ensue when these conditions are less favourable. From this standpoint, 
gemmation and tumour formation in the higher organisms, are instances 
of reversion from dominant gamogenesis to the asexual process ; and 
the genesis of malignant and other tumours is a phenomenon of the same 
order as discontinuous growth in general. 

Thus the origin of buds, as well as their subsequent development, is 
chiefly determined by the conditions of nutrition. Wherever there is an 
excess of nutritive materials, capable of being utilized for growth by the 
cells of the part, there buds may arise. 



Vegetable Tumours and Gemmation. 

From the consideration of these interesting processes, we must now 
pass to the closely allied subject of vegetable tumours ; which, as I shall 
proceed to show, are the outcome of abnormal bud evolution. 

We shall find that in these cases, the local changes are modelled after 
the processes of normal growth, and that both are subject to tne same 
laws. Changes of nutrition, causing altered growth and impaired 
development, seem to be the common aetiological factors underlying all of 
these abnormal formations. 

Their physiological prototypes must be sought in such kindred 
processes, as those above described. The clear recognition of this import- 
ant truth is likely to lead to great results, in the future development of 
this branch of pathology. 

I think there can be no doubt that the neoplastic process can be more 
satisfactorily studied in plants than in animals, owing to the absence, 
in the former, of many factors such as nerves and bloodvessels which, 
in the latter, complicate and obscure the essential nature of the process. 
In plants, the early animal embryo, and in the lower animals, all the phem> 
niena of growth go on without either nerves or bloodvessels. And so it 
is, at the outset, with all morphological variations, including bud, cancer, 
and tumour formations. In all these cases the nerves and bloodvessels 
have not the slightest direct influence. 

By bearing in mind these simple but fundamentally important con- 
siderations, we are at once able to get rid of that incubus of nineteenth- 
century tumour pathology the Broussaisian doctrine which regards 
tumour formation as an outcome of '' inflammation," rather than as an 
anomaly of growth ; for, in the vegetable world, as in the lowly organized 
part of the animal kingdom, " inflammation," in the proper sense of the 
term, is impossible, owing to the absence in these organisms of that co- 
ordinated lymph- vascular and nervous mechanism, which is the essential 



120 THE NATURAL HISTORY OF CANCER 

apparatus by which alone the phenomena of " inflammation " can be 
produced, as I shall have occasion to point out in the sequel. 

My investigations as to the nature of tumours in trees have led me to 
classify them into three main groups. 

The first group comprises those circumscribed woody nodules so com- 
monly found beneath the bark of the beech, elm, oak, cedar, holly, and 
other trees, to which the vaguely used term " knaur " is commonly 
applied. 

I have in my possession a typical example, on a small scale, from an 
elm-tree. An ovoid swelling, about the size of a Tangerine orange, 
projects beneath the bark of one of the branches. Its surface is devoid 
of buds and shoots. On section, it is seen to be composed of dense wood, 
covered with rather thickened bark. Examination of the cut surface 
shows that the tumour has been formed round two centres of development, 
each of which is surrounded by its own system of concentric woody 
laminae. These concentric systems are embedded in other woody laminae, 
derived from the investing cambium layer, and consequently disposed 
parallel with the axis of the branch. The nodules have thus been partially 
embedded in the woody tissue of the branch, and have lost their direct 
connexion with the cambium layer. A narrow ligneous pedicle connects 




FIG. 3. SHOWING FIVE CIRCUMSCRIBED TUMOURS ra THE BARK OF A HOLLY- TREE 

(NATURAL SIZE). 

the tumour with the wood of the branch. At the free extremity of the 
tumour, it is interesting to observe a separate woody nodule, the size 
of a small pea, completely isolated in the cambium layer. This may be 
taken as illustrating an early stage in the development of such growths, 
which originate from disorderly evolving adventitious buds. 

Mr. S. Paget has presented some good examples of these tumours to 
the Hunterian Museum, where they may now be seen. They are generally 
single, but occasionally several are found close together, as was the case 
in one of Paget's specimens, figured above (Fig. 3). This is described in 
the catalogue (No. 546A) as a portion of the bark of a holly-tree, with 
the cambium layer, and a small portion of the wood. Deep in the sub- 
stance of the bark are five rounded tumours composed of hard wood, 
their cut surfaces showing faint concentric lamination. At the upper part 
of the specimen, three of these have partially coalesced. They are dis- 
tinctly circumscribed in the surrounding tissues ; and there are no signs of 
any pedicles connecting them with the wood of the tree. The succeeding 
specimen (No. 546s) shows a similar tumour from a beech-tree, also devoid 
of pedicle ; and, in No. 546D, we have five similarly situated tumours, also 
from a beech-tree, with a few buds projecting from their surf aces, while here 
and there some of these buds have developed shoots or minute branches. 



TUMOURS IN VEGETABLE ORGANISMS 121 

It may be said of these tumours, that they usually present as rounded 
or ovoid swellings in the deeper part of the bark, varying in size from a 
pin's head to a cocoanut or larger. The older nodules are generally found 
lying completely isolated in the bark ; and a narrow fibro- vascular pedicle 
may sometimes be seen, connecting the younger ones with the woody 
tissues of the trunk or stem. When the pedicles persist, these formations 
are apt to become included in the woody tissue of the stem, giving rise 
to the so-called " knots " in the wood. In the earlier stages of their 
development, these tumours are occasionally surmounted by a small 
stunted branch or shoot. On section, they are found to consist of very 
dense wood, having a more or less concentric arrangement around one or 
more centres, according as their origin is from single or multiple buds. 
In most cases both pith and medullary rays can be made out. Not 
infrequently, however, their internal structure is much more irregularly 
disposed. In short, they comprise all the structural elements of the part 
whence they spring, 'but differently arranged. It would seem as if they 
might be regarded as stunted branches, in which the woody layers had been 
abnormally developed, in compensation for the curtailment in length 
and in other respects. 

Lying at first isolated in the bark, these nodules increase in size at 
the expense of the surrounding nutritive materials. Hence, it often 
happens that their growth on the side of the cambium outruns that on 
the other side, where the nutritive supply is less abundant, so that a certain 
eccentricity in the arrangement of the laminae is produced. Destruction 
of the bark which usually covers them in, whether as the result of injury 
or some other cause, such as pressure of the growing nodule itself, renders 
this tendency to increased growth on the side of the cambium still more 
marked ; for, we then see complete cessation of growth at the exposed sur- 
face, which may even decay in consequence, while the side of the nodule 
next to the wood, owing to the proximity of the cambium, still continues 
to increase. 

These tumours, as Dutrochet long ago discovered, first appear as very 
small buds in the cellular tissue of the bark ; where they originate from 
unspecialized cells, quite independently of the wood of the trunk. In 
short, almost all of those who have specially studied this subject, are now 
agreed in ascribing the origin of these tumours to disorderly growth of 
adventitious or dormant buds. There is no doubt that buds may remain 
in a quiescent state for years ; and then, under the influence of favourable 
conditions, develop renewed activity, the result being either a shoot, a 
branch, or one of these tumours. 

Such being their origin, it is not surprising to find these tumours, like 
buds, possessed of distinct individuality ; and capable of reproducing their 
like in the form of buds, shoots, branches etc. It even occasionally 
happens that, in their young state, these anomalous formations may be 
used for propagating the species asexually. 

In all of the above instances, the outcome of the morbid process is the 
production of a highly organized, circumscribed, new formation, analogous 
to the fibromas, lipomas, and other similar non-malignant new growths 
of human and animal pathology. 



122 THE NATURAL HISTORY OF CANCER 

Before entering on the consideration of the second group of tumours 
in trees, I must first of all offer a few observations with regard to certain 
intermediate formations of the nature of local overgrowths. I have often 
remarked in various trees the presence of hypertrophic branches ; and, in 
several instances, I have seen localized hypertrophies involving the whole 
thickness of portions of the branches of such trees as the elm, lime, and 
oak. These conditions may be compared with the hyperostoses of 
human pathology. They occupy an intermediate position between the 
hypertrophic and neoplastic processes. Such conditions arise at an early 
stage of development, in consequence of excessive activity of the cambium 
at the affected part. These local overgrowths generally present as elon- 
gated protuberances covered with bark, their diameter being many times 
greater than that of the branch or stem whence they grow. On section, 
they consist of hard wood, the concentric layers of which are unusually 
thick and very obvious, while the medullary rays, extending from the 
centre to the periphery, are but thin. Trecul has figured a fine example 
of this kind from a birch-tree. 

The second group, comprising the continuous tumours, are comparable 
with the exostoses of human pathology. These present as woody out- 
growths of the trunk or branch. They often attain great size, as in the 
specimen figured on the next page (Fig. 4), which measured 16 by 1 1 inches, 
and weighed 67 pounds : the diameter of the branch on which this tumour 
grew, was 4| inches on the proximal and 4 inches on the distal side. 

The general characters of these growths may be gathered from the 
subjoined brief description of this specimen, which was removed from one 
of the largest branches of a young elm-tree probably about thirty-five 
years old on the main trunk of which was another similar growth, the 
tree being in other respects healthy. It was completely covered with 
rather hypertrophied bark, and two small branches grew from its surface 
near the periphery. On longitudinal section, it was found to consist of 
very hard wood, directly continuous with that of one side of the branch 
whence it grew. The laminae composing the tumour showed a concentric 
arrangement of outcurved, irregularly wavy layers ; Avhile those of the 
branch itself appeared longitudinal (Fig. 4). Moreover, the former were 
many times thicker than the latter ; and in the broadest part of the 
tumour I was able to count twenty-six of these layers. A singular 
feature in this case is, that a portion of the tumour had grown completely 
round the healthy part of the branch, outside the bark ; and had then 
blended with the main tumour on the opposite side, so as completely to 
encircle the branch on which it grew. This specimen was removed from 
a tree growing in a damp meadow, where the soil was heavy, and saturated 
with sewage-polluted water. An adjacent elm, of about the same size, 
presented a single similar outgrowth on its main trunk. 

Similar tumour-like growths have occasionally been seen even on the 
root of various plants e.g., Taxodium distichum, Cupressus macaro- 
carpa etc. 

Dutrochet describes these growths as arising in much the same way 
as the discontinuous knaurs, by a kind of bud formation, in the deeper 
part of the cambium layer ; hence their connexion with the woody tissues 



TUMOURS IN VEGETABLE ORGANISMS 123 

of the stem is well secured from the outset, and so it is never lost. These 
tumours may be regarded as stunted, abnormally evolved, branches. 

Composite tumours of this kind, resulting from a group of buds 
instead of a single one being concerned in the origin of the malady, are 
by no means unusual ; and thus very dense formations are often developed 
on elm stems, which are in much demand by cabinet-makers, on account 
of the remarkable patterns presented by the diversely contorted arrange- 
ment of their woody fibres. 

Such being their structure and mode of origin, the tumours of this 
group may fairly be compared with the exostoses and analogous con- 
tinuous tumours of human pathology ; and, like them, they are highly 
organized. 




FIG. 4. A CONTINUOUS TUMOUR COMPARABLE TO AN EXOSTOSIS FROM AN ELM- 
TREE, IN LONGITUDINAL SECTION. , 

In the third group, I include all those new formations, called by the 
French broussins, whose distinguishing peculiarity is the very free and 
continuous formation of proliferous buds, shoots, and stunted branches. 
The term " burr v might very well be employed as the English synonym 
for these growths, which often attain enormous proportions. 

I have seen an old lime-tree, with a huge excrescence of this kind 
densely studded with buds, shoots, and brushwood, growing at the junction 
of the trunk with the main branches. 1 

Three other aged lime-trees in the immediate vicinity were similarly 
affected. In all of these cases, the general health of the trees appeared to 

1 This growth is figured in my book on " The Principles of Cancer and Tumour 
Formation," Fig. 15, p. 98. 



124 THE NATURAL HISTORY OF CANCER 

have deteriorated considerably, as indicated by numerous dead branches, 
etc. In the same neighbourhood I have seen similar growths on elm, 
hornbeam, and other trees, one of which is figured on the next page (Fig. 5). 
The trees of this particular locality are, in fact, remarkably prone to these 
growths, and to various other morphological anomalies. Most of these 
trees are old, and of large size. For a long period they have been left quite 
uncared for innocent of the acts of forestry. The situation of the 
locality is peculiar. It forms part of a shallow depression, lying below the 
slope of a hill. A large brook, the natural watershed of the neighbour- 
hood, runs sluggishly through the low-lying part. In its course, it here 
forms several large lacustrine ponds, owing to the slightness of the 
gradient. The water is highly charged with sewage matter. Clay for- 
mation underlies the whole neighbourhood, and forms the bed of the 
watercourse, while a layer of loose gravel rests on the clay. It results 
from this arrangement, that the whole of the depressed area is thoroughly 
saturated with sewage-contaminated water ; and its vegetation has 
consequently long been abnormally nourished. 

A specimen illustrating the same type of disease, from one of the chief 
branches of a hornbeam-tree, is shown in Fig. 5. The growth is composed 
of innumerable, densely massed buds, a few of which have developed into 
shoots and twigs. Almost the whole circumference of the branch, for a 
distance of 15 inches, is surrounded by the growth. On section, the 
subjacent woody tissue of the branch, corresponding to the seat of the 
disease, is seen to be double its normal thickness. The wood here is very 
dense and of irregular formation, except in the central part ; and, between 
the two, there is no definite line of demarcation. Interspersed in this 
dense wood are detached fragments of bark ; and, in several places, long 
processes of bark penetrate deeply into the wood. This great thickening 
and irregular formation of 4 the wood, are due to the exuberant and' 
irregular flow of sap, caused by the abnormal and proliferous gemmation, 
which is the essential element of the disease. 

I have seen similar tumours on elm and other trees. 

The peculiarity of growths of this kind, consists in the immense number 
of buds which develop adventitiously in the cambium layer of the affected 
part ; when, they either remain dormant, or forthwith develop into shoots 
or stunted branches. The aggregation of these structures causes retar- 
dation and irregularity in the flow of the sap ; whence the exuberance of 
the growth, and the curious markings produced in the wood. Moquin- 
Tandon mentions having seen a grafted ash, in the Botanical Garden of 
Toulouse ; where, below the graft, a large growth of this kind formed, 
from which proceeded over a thousand small, densely packed interlacing 
branches. 

The production by these growths of large quantities of proliferous, 
lowly organized, cellular tissue, which subsequently undergoes some 
imperfect developmental changes mimicking the structure of the part 
constitutes the nearest approach in vegetable pathology to the malignant 
tumours of human and animal pathology. The absence in these vegetable 
tumours of anything like the disseminativeness of human malignant 
tumours, may be urged as an objection to this comparison. But to this 



TUMOURS IN VEGETABLE ORGANISMS 



125 



the answer is, that in the absence of a highly specialized lymph-vascular 
system, capable of transporting the proliferous cells, such disseminative- 
ness is not to be expected ; and that it is to deficiency in this respect 
rather than to any essential difference in the nature of the morbid process 
that the absence of disseminativeness in vegetable tumours must be 
ascribed. For, as I have previously indicated, the essential feature of 
malignancy is not disseminativeness, but rather the indefinitely sustained 
activity of certain lowly organized cells, which grow and multiply 
independently, without ever reaching the highest grade of organization. 




FIG. 5. A MALIGNANT TUMOUR, DENSELY STUDDED WITH SHOOTS AND STUNTED 
TWIGS, FROM ONE OF THE CHIEF BRANCHES OF A HORNBEAM- TREE. 

With regard to the aetiology of these growths, beyond what has been 
above indicated, all that I need now say is, that I have been unable to find 
any evidence as to their being due to parasites or other irritants ab extra. 



Galls and Other Vegetable Pseudo-plasms. 

Even in human and animal pathology it cannot be denied, that 
irritative conditions may elicit formative reactions ; and, in the vegetable 
world, even among highly evolved forms, reactions of this kind are of 
frequent occurrence as well as of marked character. This is exemplified in 



126 THE NATURAL HISTORY OF CANCER 

the case of galls, which may comprise not only structures similar to those 
met with in the parts whence they originate, but also other structures 
which do not occur there ; thus, as Beyerinck has shown, cells which are 
usually only developed in the bark, are frequently found in some leaf- 
galls etc. 

The formation of galls is certainly a very interesting phenomenon, 
which has yet to be fully explained, as have also the analogous processes 
underlying bud, cancer and tumour formation, and other morphological 
variations. 

It was formerly thought that galls arose in consequence of excessive 
local cell growth and proliferation, excited by a virus instilled into wounds 
made by insects in depositing their ova ; but the researches of Adler and 
Beyerinck have shown the inadequacy of this conception. They have 
conclusively proved that galls are due, not to the sting of the parent 
insect, but to the activity of the larva after it has been hatched. 

Although most gall-producing insects do actually wound the tissues of 
plants in depositing their ova, yet no galls result from the lesions for 
instance, in the case of the common oak-apple gall, the Biorhiza aptera 
deposits its ova in punctures in the bud early in the winter, but no gall 
formation occurs until the following spring, when the larvae become 
active ; similarly, when no ova are deposited in the punctures made by 
the parent insect, no gall is formed ; and the result is just the same when, 
although ova have been deposited, the embryos fail to develop or die 
early ; and, when the larva dies, the gall ceases to grow. From these 
considerations it follows that the gall is the reaction of the plant to some 
X stimulus proceeding from the larva, the nature of which is still under 
discussion. 

It is hardly likely that the mere presence of the larva, acting as a 
foreign body, or its movement^ per se, can be the real causative factors of , 
these formations, otherwise there would not be such extraordinary 
diversities in the resulting galls those produced by the larva of each kind 
of insect presenting structural peculiarities which are quite sui generis. 
Thus, on the oaks of Central Europe alone, nearly a hundred different 
kinds have been discriminated, all produced by different but closely 
allied species of gall wasps. 

Of like import is the fact, that no one has yet succeeded in producing 
galls experimentally, although attempts of this kind have not been lacking. 

Another indication pointing in the same direction comes from Adler 's 
interesting discovery, that galls produced by the same insect, in the 
alternating phases of its heterogenesis, are markedly different : thus, the 
-^ common currant gall of the male flower of the oak, is the product of one 
phase (unisexual) of the existence of a gall-producing insect, which in 
another phase (bisexual) causes the red spangle gall of the under surface 
of the oak leaf. 

It seems to follow from these considerations, that the stimulus in 
question must be some specific secretion of the larvae themselves ; and 
Beyerinck considers that the salivary secretion is the one specially 
indicated, the active principle perhaps being some special fermentative 
or allied bio-chemical process, not as yet discriminated. However this 



TUMOURS IN VEGETABLE ORGANISMS 127 

may be, it is evident that -very slight differences in the nature of the 
causative stimulus, determine widely different morphological results in 
the produced gall ; this is specially obvious when, as sometimes happens, 
several quite different galls, caused by as many different parasites, are 
formed on the same leaf. 

In discussing this subject, Darwin remarks : "As the poisonous 
secretion of insects belonging to various orders, has the special power of 
affecting the growth of various plants ; as a slight difference in the nature 
of the poison suffices to produce widely different results ; and, lastly, as 
we know that the chemical compounds secreted by plants are eminently 
liable to be modified by changed conditions of life, we may believe it 
possible that the various parts of a plant might be modified through the 
agency of its own altered secretions. With such facts before us, we need 
feel no surprise at the appearance of any modification in any organic 
being." 

As exemplifying these remarks, we may profitably recall and contrast 
the mossy rose-gall, the product of extrinsic parasitic stimulation ; and 
the mossy outgrowths of the calyx of the moss rose, spontaneously arising 
as the result of unknown intrinsic changes. 

. The willow galls caused by a species of Nematus also illustrate the 
free formation of epidermal trichomes, in response to parasitic irritation. 

Another remarkable feature about such galls as we are now concerned 
with is, that the form assumed by them is "beneficial to the parasite rather 
than to the tree-host ; so that it appears as if we must ascribe this effect 
to a specific stimulus proceeding from the larva, which these formations 
are obviously adapted to protect, support, and nourish ; and it is difficult 
to escape the conclusion, that this stimulation is in some way connected 
with the feeding of the larva on the cells of the plant by which it is sur- 
rounded. As for the reaction on the part of the tree-host, this may be 
regarded as an exaggerated and specifically modified outcome of the 
reparative process. Some remarkable examples of the influence of the 
stimulus in directing this reaction for the advantage of the parasite, are 
seen in the case of those galls out of which the parasite is unable to eat 
its way, when the time for escape has come ; for such galls then dehisce, 
as many fruits do, and so allow the parasite to escape. 

In this connexion, however, it should be noted that among the immense 
number of galls, there are some in which host and parasite live together in 
a manner that is mutually beneficial (symbiosis) ; while, in others, the joint 
existence is very harmful or even fatal to the plant-host. 

As an example of the former condition, the remarkable growths 
occasioned by parasitic ants, in the so-called " ant plants " (Myrmecodia 
etc.), may be cited ; which Beccari and others consider to be indispensable 
for the healthy development of such plants the latter protecting the 
ants, which in their turn protect the plant. 

In like manner the galls formed on the roots of leguminous plants, 
owing to the agency of parasitic fungi, contribute to the well-being of 
the plant, by elaborating and storing nutritive materials for its use. 

In these cases, we have evidence that plants subjected to certain 
stimuli of vital origin respond thereto, not merely by local hypertrophy, 



128 THE NATURAL HISTORY OF CANCER 

but also by profound alterations in their morphological and physiological 
dispositions, which ordinary mechanical stimuli are unable to elicit. 

The earliest changes in gall-formation consist in active growth and 
proliferation of the merismatic cells " blastem " immediately sur- 
rounding the parasitic embryo ; these cells from the first respect the 
included larva, for which in the course of their subsequent development 
a free cavity is formed the so-called larval chamber ; and they subse- 
quently undergo developmental differentiation, much after the manner 
proper to the normal ontogeny of the affected part. 

It is a noteworthy fact that some galls, like abnormally evolving 
adventitious buds, may be used for purposes of propagation. 

Gall-producing parasites are exceedingly numerous and of many 
diverse kinds, both animal and vegetable forms being represented ; but 
the commoner and more conspicuous galls are generally caused by insecta 
most orders of this class comprising some gall-producing representa- 
tives, of which CynipidoB and Acari are among the commonest ; fungi are 
also responsible for many e.g., the " apple canker," due to Nectria 
ditissima ; and, besides these, various protophyta and protozoa, such as 
the Plasmodiophora brassicce, which cause the tumour-like swellings on 
the roots of cabbages etc. 



CHAPTER VII 
THE GENESIS OF MALIGNANT TUMOURS 

Historical Review. 

THE ancients of the classical period divided tumours into three great 
classes : Tumores secundum naturam, supra naturam, prceter naturam. 
Physiological enlargements were included in the first ; the second com- 
prised swellings due to the displacements of natural parts ; while the 
third embraced all other swellings a miscellaneous assemblage, com- 
prising all that we now include under the term " tumour," and many 
other conditions besides. 

By Galen l and his followers the tumours prceter naturam were believed 
to result from the accumulation of one or other of the four humours, each 
of which generated its corresponding kind of tumour. Of these humoral 
tumours, those of the group called " scirrhous " which embraced cancer, 
and nearly corresponded with that we now understand by the word 
" tumour " were believed to arise from the accumulation of atrabile 
(Cancer ab atrabile). 

After the long centuries of ignorance, stagnation and superstition, 
that followed the overthrow of the Roman Empire and classical learning, 
by swarms of barbarian warriors, the humoral theory at length emerged 
from the wreck not appreciably altered. 2 

Indeed, it was not until the discovery of the circulation of the blood, 
early in the seventeenth century (Harvey, Malpighi, Leeuwenhoek, and 
others), that this doctrine was overturned. 

In place of the humours, the blood was now regarded as the true source 
of the disease. 

Early in the eighteentli century the Cartesians, with Boerhaave at 
their head (Morbus est vita prceter naturam), ascribed the origin of 
tumours to the newly discovered lymph a derivative of the blood : 
cancer they regarded as the outcome of vitiated, depraved, or degenerated 
lymph. 

Doctrines of this kind continued to hold sway, until the time of Bichat 
at the end of the eighteenth century. 

With the advent of the illustrious founder of biology, we begin to 
discern the first rudiments of modern conceptions emerging from the 
ancient chaos. The philosophical insight of Bichat enabled him 

" De tumoribus prseter naturam." 

2 As a historian of medicine has remarked : " Greek medicine of the fifth century B.C. 
seems to be almost of yesterday ; whereas, English medicine of the twelfth century of 
our era, is as alien and grotesque to our thought as the demonology of the Chaldeans." 

129 9 



130 THE NATURAL HISTORY OF CANCER 

without the aid of the microscope and relying only on gross appearances 
to decompose the organism into its elementary tissues ' and organic 
systems. " Every tissue," said Bichat, " has its own diseases." 

This was a great advance on previous ideas ; and it is on this basis 
that the modern anatomico-pathological study of tumours rests, which 
the labours of Laennec, Andral, Louis, Bayle and Cruveilhier in the same 
direction subsequently strengthened and extended. 

Thus Bichat anticipated and prepared the way for the cell theory 
the culminating point of modern biological progress although due 
acknowledgment of this his great achievement has, I think; never before 
been accorded to him by English, American, or German pathologists. 

At this juncture, early in the nineteenth century, the current of 
thought was suddenly interrupted and changed, by the appearance on 
the scene of the impetuous Broussais. 1 His doctrine was that all tumours, 
including cancers, w r ere but forms of chronic inflammation, consequent on 
organic irritation. The extreme simplicity, comprehensiveness, and 
positiveness of this crude generalization suddenly sprung on a scientific 
world, hesitating between the old humoral doctrines and the nascent 
anatomico-pathological tentatives captivated every one ; and the 
Broussaisian system, in an incredibly short time, became supreme. 

But its supremacy was short-lived. What more than anything else 
contributed to its downfall, was the application of the microscope to the 
study of living things. To this instrument and its revelations, we are 
indebted for the two great doctrines of modern medical science the 
cell theory and the germ theory. The far-reaching importance of the 
revolution thus effected is, even now, by no means duly appreciated. 
It might be thought that the history of the invention of an instrument, 
which has done so much to enlarge the field of knowledge as the micro- 
scope, would be a theme for every one ; but, as a matter of fact, the 
discovery is shrouded in obscurity. It is believed that the earliest 
compound microscope was made by the Janssens father and son 
spectacle-makers of Middelburg in Holland, near the end of the sixteenth 
century. One of their instruments was exhibited in London by Drebbel 
of Alkmaar early in the seventeenth century (1617). Unfortunately it 
was imposible to see clearly with this instrument, when high magnifying 
powers were used, owing to the disturbing influences of chromatic and 
spherical aberration ; hence the compound microscope was at first merely 
a scientific toy. It took more than two centuries to overcome these 
defects. At length, early in the nineteenth century thanks to the skill 
of Selligues, Chevalier, Tully, Amici, Lister, and others these difficulties 
were surmounted. In 1830, a real serviceable compound microscope was 
at last produced ; and with its aid naturalists, shortly afterwards, began 
to explore the minute structure of organic forms, as Newton had long 
before predicted. Thus the science of histology was born, which 
subsequent improvements in optical appliances and a better technique, 
have advanced to its present remarkable state of perfection. 

With this new aid the cellular structure of organized beings was ere 
long discovered. For the famous cell theory which must be ranked 
1 " Traite des Phlegmasies chroniques," 1808, etc. 



THE GENESIS OF MALIGNANT TUMOURS 131 

among the most important steps by which the science of biology has 
ever been advanced we are indebted to the vegetable morphologist 
Schleiden ; and shortly afterwards Schwann demonstrated the applica- 
bility of his generalizations to the animal world (1838). In the very same 
year the publication of J. Miiller's important work on the origin of 
tumours, 1 established the cellular nature of cancer and other neoplasms. 
Modern conceptions as to the pathogenesis of tumours date from this 
period. 

Miiller believed that the constituent cells of tumours were derived 
from a formative fluid, exuded from the blood (blastema) ; which was 
nothing but the coagulable lymph of Hunter, under another name. He 
ascribed the origin of cancer and other neoplasms, and their variations 
inter se, to aberrations of the force inherent in this primordial substance, 
causing the resulting cells to deviate from their usual evolution. Miiller 
also strongly insisted on the correspondence between the development 
from the embryo, and the pathological neoplastic process : " It is one 
and the same power which, being maintained continuously from the germ 
to the latest period of life, determines all organic formation." 

The pathological cells, he maintained, differed from the physiological 
cells only in respect to the degree of evolution ultimately attained. The 
division of neoplasms into two great classes, according as their structure- 
resembled the normal tissues (homologous), or differed from them 
(heterologous), Miiller completely rejected. " It is evident," he says, 
" that no division of pathological structures into homologous and hetero- 
logous can be established. Such a classification is formed without anv 
knowledge of the structure of morbid growths., and is founded on blind 
gratuitous hypothesis. The most innocent growths do not differ in their 
minute elements, nor in their origin, from the most malignant ones." 

The establishment of the cell theory gave an immense impetus to 
pathological histology, and a vast mass of new data soon accumulated. 
Virchow, 2 some twenty years later, pounced upon these ; and, with 
wonderful insight, skill, and energy, elaborated them, together with 
independent observations, into a kind of new cell theory ,. which still 
prevails. Virchow's influence on modern conceptions has been so great, 
that it will be of interest to trace the genetic relationship of his ideas with 
those of his predecessors. It may be said that he adopted the cell theory 
in its entirety, as laid down by Miiller, with the single important excep- 
tion, that he completely exorcised the blastemal origin of cells. It was 
just this omission that chiefly constituted the novelty of his system. 
Instead of a hypothetical blastema, he substituted the famous formula 
'' Omnis cellula & celluld" = " Where a cell arises there a cell must have 
previously existed, just as an animal can spring only from an animal, 
and a plant from a plant." Thus the doctrine of continuous cellular 
development, that had been established by Remak for the normal tissues, 
became the basis of Virchow's neoplastic pathogeny. 

Another important respect in which Virchow's cellular pathology of 
tumours differs from that of his predecessors, is in the addition to it of 

1 " Ueber den feineren. Bau und Formen der krankhaften Geschwiilste," 1838. 

2 " Cellular Pathologic," 1859. 

92 



132 THE NATURAL HISTORY OF CANCER 

the whijom extinct Broussaisian doctrine of irritation and chronic 
inflammation. 1 Nowhere in Virchow's works have I met Avith any attempt 
to explain the compatibility of this irritation hypothesis, with the doctrine 
he also adopted, of the correspondence between the embryonic and neo- 
plastic developmental processes. In my opinion, these views are abso- 
lutely incompatible ; and this incompatibility constitutes a serious flaw 
in Virchow's neoplastic pathogeny. I believe that tumour formation is 
the outcome of formative hyperplasia (e.g., growth), and not of inflam- 
mation. By most pathologists these two fundamentally distinct processes 
are confused together, and treated as being one and the same ; whereas, 
my belief is, that they are in every respect different and distinct. Inflam- 
mation is the outcome of extrinsic causes ; whereas, the causes which deter- 
mine neoplastic hyperplasia are, as I shall show in the sequel, mainly 
intrinsic. Moreover, the two processes are morphologically distinct. 
In short, the morphological and biological characters of tumours show, 
that neoplastic pathogenesis is something quite different and distinct 
from all inflammatory processes. As Billroth has remarked, 2 if we once 
allowed the principle of the correspondence between the embryonic and 
neoplastic processes to be lost sight of, we should necessarily fall back 
" into the old chaos of parasites and pseudo-plasms," which is exactly 
what we are now experiencing. 

Of late, owing to a variety of causes, Virchow's doctrines have 
undoubtedly lost ground. For this lapse, Virchow himself is to a large 
extent responsible. As is well known, his dogmatical and didactic mind 
entertained deeply rooted aversion for all kinds of theories and hypotheses. 
It was this lack of scientific imagination, that caused him to go out of his 
way, in a realty extraordinary manner, to prevent his followers from 
assimilating the new facts and principles brought to light by modern 
biological progress, in connexion with the doctrine of evolution. Another 
consideration that tended to confirm him in this opposition, was the fact 
that in the domain of neoplastic pathology, wherein his ideas concentred, 
evolutional conceptions seemed to have but little application ; for most 
pathological neoplastic phenomena are the outcome of the failure or 
undoing of evolution. Hence, while the rest of biology has been revo- 
lutionized, the cellular pathology has remained stationary. 

So far as the pathology of neoplasms is concerned, in my work on 
" The Principles of Cancer and Tumour Formation " (1888), I endeavoured 
to repair Virchow's error, by laying the foundation of a modified cellular 
pathology in harmony with modern biology ; and although this \vork has 
hitherto received no recognition from contemporary pathologists, pre- 
occupied with various kinds of will-o'-the-wisps I confidently look 
forward to the time when the conceptions there embodied will be generally 
accepted, as furnishing the only really scientific basis for explaining the 
phenomena of pathological neoplasia ; which, as I have there set forth, is 
at the bottom essentially a biological problem. Hence, nothing will be 
more conducive to this end, than the wider spread of biological knowledge 
and conceptions among modern pathologists ; who are, even now, for the 

1 " Die krankhaften Geschwiilste," Bd. i., 1863 (third lecture). 

2 "Surgical Pathology," 1879, p. 600. 



THE GENESIS OF MALIGNANT TUMOURS 133 

most part, very deficient in this respect, as so many recent publications 
testify. 

Another circumstance that has tended to weaken Virchow's authority, 
is the large measure of success accorded to a modification of the cellular 
theory propounded by Cohnheim, 1 according to which tumours are derived 
from displaced fragments of the germinal matrix, sequestered during the 
earliest period of embryonic life. 

In this, its original primitive form, the theory was only capable of 
very limited application ; but, as subsequently modified, so as to include 
sequestrations of the various tissues and organs arising at later periods of 
embryonic ,and post-embryonic life (" rests ")., it embraces a very large 
number of facts relating to tumour genesis. 

Moreover, in this way attention was directed to the frequent association 
of tumour formation with various kinds of developmental irregularity a 
very important indication. 

That a considerable proportion of malignant and non - malignant 
tumours actually do arise in this connexion, I have convinced 
myself. 

There are, in fact, good reasons for believing as I shall presently 
show that tumours are specially apt to arise wherever cells, still capable; 
of growth and development, are present ; and, that they are most prone 
to originate, where such cells most abound. 



The Present Controversy. 

But what more than any other recent occurrence, has undermined the 
authority of the cellular neoplastic pathogeny is the widespread belief, 
that tumours will ultimately turn out to be of microbic origin. In short, 
it is evident, that out of the confusion of a transitional period, but two 
conceptions as to the origin of tumours have emerged the one based on 
the cell theory, and the other on the microbe theory ; and henceforth the 
struggle must be between these two. Briefly stated, the question 
now is : Do cancers and other tumours arise through modification 
of the formative process.; or, are they the outcome of the inflamma- 
tory process, owing to the intrusion of microbes, or other irritants 
ab extra ? In other words : Are they essentially of intrinsic or extrinsic 
origin ? 

Those who incline to the former alternative, look to the biological 
properties of the cells of the affected part, for the key of the problem : 
whereas, the other side, refer all the essential phenomena of the disease to 
the activity of parasitic microbes, or other external irritants. 

When the issues are thus plainly stated, the great importance of 
choosing a working hypothesis at once becomes apparent ; for, of the 
two alternatives, only one can be true. My own belief is, that tumours 
arise mainly from the abnormal play of forces generated within the body ; 
and it is to this aspect of the question that I now propose to direct 
attention. 

1 " Vorlesungen iiber allgemeine Pathologic," 1877. 



134 THE NATURAL HISTORY OF CANCER 

The General Theory of Intrinsic Pathogenesis. 

It has hitherto been customary, as I have previously intimated, to 
regard tumour formation as an isolated pathological entity, having no 
connexion with other biological processes. This seems to me to be a 
fundamental mistake ; for, the first step towards a rational interpretation 
of tumour genesis from the biological standpoint, must necessarily be the 
discovery of its true affinity. Now, it is in morphological variation in 
general, as I have previously indicated, that this affinity is to be found. 
Indeed, what is variation but a novel kind of cell multiplication ? And 
what is tumour formation but a special variety of this novelty ? And is 
not every variation, as Virchow suggested, essentially pathological ? 
The answer to all these queries as we now see is, as implied. Variation, 
< mutation, and tumour formation, these are but different manifestations 
of one and the same process. 

In the preceding chapter, I have traced the connexion between these 
kindred manifestations, as it occurs in vegetable organisms ; where 
tumour formation was shown to be an outcome of abnormal gemmation, 
which is a form of agamogenesis. 

In human and animal organisms, the biological significance of tumour 
formation is precisely the same, as I have shown at some length in my 
book on " The Principles of Cancer and Tumour Formation." 

In that work I have adduced reasons for believing, that there is no 
fundamental, specific distinction between such apparently varied bio- 
logical processes, as the various modes of reproduction gamogenetic and 
agamogenetic, the processes of repair, maintenance and new formation 
of tissues, the reproduction of lost parts, and the various morphological 
variations including bud, cancer and tumour formations. 

All of these apparently so different phenomena, are there shown to be 
merely protean modifications of one common process, which underlies and 
is the cause of them all to wit, cell growth and proliferation. The 
particular outcome of the process in any given case, is shown to be due to 
the influence of the conditions of nutrition understanding by this term 
the whole of the material changes wrought in the organism through its 
relations with the surrounding outer world. This being so, it is easy to 
understand how, under favourable conditions, certain cells may take on 
independent action, growing and multiplying, without regard to the 
requirements of adjacent tissues, and of the organism as a whole. Thus 
the various pathological new formations arise. From the biological 
standpoint, then, tumour formation must be regarded as a phenomenon 
of the same order as reproduction in general ; that is to say, as a special 
form of overgrowth of the individual. 

The nearest congeners in the biological domain to the tumours of 
human and animal pathology, must be sought in the suddenly occurring, 
non-adaptive new formations, known to biologists as " sports," " bud 
variations," " spontaneous variations," " discontinuous variations," etc., 
all of which abrupt transformations may be conveniently comprised under 
7 the term " mutation," as suggested by De Vries. 1 

1 Although the term " mutation " belongs to De Vries, the mutation theory was 
founded by Bateson (" Variation," 1894). 



THE GENESIS OF MALIGNANT TUMOURS 135 

Moreover, all of these kindred processes may be regarded as being 
dominated by a common aetiological factor, since, in ultimate analysis, 
they may be ascribed to the cumulative effects of changed conditions of 
existence of which, in the case of animals, the most important items 
probably are excess of food, changed environment, and want of proper * 
exercise. 

Another question of fundamental importance remains to be con- 
sidered, before we can proceed to the study of the process of tumour 
genesis ; and this is the question as to the relations of the somatic and 
germ cells to one another, and to the organism as a whole. 

After very thorough study of the chief types of reproduction through- 
out the organic world, Herbert Spencer 1 concluded that we are justified 
in assuming, that every component cell of the multicellular organisms 
has the inherent power, under favourable conditions, of developing into 
the form of the parental organism : so that each cell may be regarded as 
potentially the whole organism. According to this conception with 
which Darwin and Haeckel were in agreement the reproductive proper- ^ 
ties manifested by somatic and germ cells are the same in kind, and 
differ only in degree. 

This doctrine has been strenuously attacked by Weismann and his 
followers, who have founded their theory of heredity by continuity of 
the germ-plasm, on the assumption that the reproductive properties of 
somatic and germ-cells are specifically different : at least, this was the 
initial conception ; but, when it was subsequently demonstrated that in 
many plants and animals (e.g., mosses, hydra etc.), almost any cell 
sufficed for the reproduction of the entire organism, this difficulty was 
met by the supplementary hypothesis of " accessory " germ-plasm 
<" idioplasm "), which in such cases was supposed to have become diffused 
throughout the soma protoplasm. 

But such a conception dispenses with the necessity for the original 
"hypothesis ; for, if all or most of the soma protoplasm can manifest this 
reproductive capacity, it is surely much more likely that this property is 
inherent in its structure, rather than that it is due to the intrusion of 
hypothetical " germ-plasm " ab extra. 

Thus, in my opinion, the validity of Spencer's conception remains 
unimpaired. As I have fully set forth the very convincing evidence 
supporting this conclusion, in my work on " The Principles of Cancer and 
Tumour Formation," 2 there is no need for me to enter into detailed 
restatement of the same here. For our present purpose; it will suffice if I 
recall, in the briefest manner possible, some of its chief features. From 
this standpoint, what are we to think of the fact that a single scale from 
the leaf, stem, or root of a plant, suffices for the reproduction of the whole 
organism (mosses, begonia etc.) ; or that nearly as small a particle of 
the Hydra and other animals, is able to reproduce the whole organism ? 
Does not the whole history of adventitious gemmation in plants, as 
detailed in the preceding chapter, testify against fundamental difference 
between somatic and germ cells ? Is it not the same with gemmation in 

1 " Principles of Biology," 1884. 

2 Chap, xi 



136 THE NATURAL HISTORY OF CANCER 

animals, with asexual reproduction, with metagenesis, and with partheno- 
genesis ? Do not the phenomena of repair, and the reproduction of lost 
parts, testify to the same effect ? I say that they do. 

The very remarkable manner in which the majority of British 
biologists were at once captured by Weismann's fascinating intellectual 
divagation, is one of the features of the history of the scientific life of the 
period : it is likely to rank with the celebrated heresy of Liebig, as to the 
non-microbic nature of fermentation, which retarded the advent of the 
microbe theory for such a lengthy period ; and with the vagaries of 
Cuvier, which caused his curious hypothesis as to the origin of species, to 
be preferred to the more truthful conceptions of Lamarck, and so retarded 
the progress of modern biology for more than half a century. As the 
veteran R. Owen, 1 so well remarked, when these biological speculations 
first began to swarm : " If science is to retain its strength, it must keep in 
touch with the solid ground of observation. In reading some of the 
biological literature of the day, I sometimes rub my eyes, and wonder 
whether I am not dreaming of the good old days of the Natur-philosophie.'' 
To be quite frank, I regard the great body of scientific truth relating to 
growth, reproduction, variation, heredity, and allied biological problems, 
as being on the whole more fully enshrined in the works of Spencer and 
his great lieutenants Darwin and Haeckel, than in any other publications : 
and it is mainly on this basis that I have built up my doctrine of tumour 
formation. 

In the genesis of tumours, as in the genesis of other organic structures, 
I believe we must take into consideration two factors the cells whence 
they originate and the force that regulates the cellular activities. 

With regard to the cells, although each is largely dependent upon 
others, yet at the same time each manifests a certain independence or 
autonomy. In the special changes underlying pathological new forma- 
tions, the autonomy of the cells plays an important part. It is quite 
certain that somatic cells are possessed of far greater reproductive power, 
than they ever ordinarily manifest. Evidence of this is seen in the 
processes of repair and regeneration, in the changes that take place at 
puberty and in connexion with pregnancy when the breasts and uterus 
undergo such remarkable metamorphoses in the phenomena of com- 
pensatory hypertrophy, and in a variety of other processes. Strange to 
relate, this wonderful reproductive capacity, which enables us to under- 
stand how a single cell may originate even the largest tumour extant, has 
received but scant attention from pathologists in explaining the neoplastic 
process. That the reproductive activity actually manifested by somatic 
cells usually falls so far short of their potentiality, is believed by Spencer 
to be due to the restraining and modifying influence exerted by the 
whole organism on their protoplasm ; which is thus compelled to the 
performance of comparatively subordinate, modified functions. In 
the performance of these special duties, most of the protoplasm is 
metamorphosed and used up. Hence, in proportion as the cells are 
highly specialized, their reproductive function is either greatly reduced 
or altogether lost. But, in the higher organisms, certain cells never 
attain a high degree of development ; they remain in a lowly organized 
1 Owen's " Life," vol. ii., p. 330. 



THE GENESIS OF MALIGNANT TUMOURS 137 

condition, and serve according as they are more or less unspecialized 
either as germs for reproducing the entire individual, or for forming and 
maintaining the various tissues and organs. Cells of this kind abound 
in all parts growing and capable of growth. These are the sources 
whence cancer and tumour germs are derived. 

In the ordinary course of organic evolution, the processes of cell 
growth and multiplication go on, until the amount of structure proper 
to the organism has been produced ; then they are restricted within 
certain limits. In the healthy organism, this state of balanced equi- 
librium is maintained throughout the whole life of the individual. Herein 
is evidence of a force regulating the growth and development of the tissues 
and organs in relation to each other, and to the organism as a whole. In 
order to account for this, it may be assumed that, by a kind of selective 
assimilation, the molecules of each part have the power of moulding the 
adjacent nutritive materials into molecules, after their own kind. " Like 
units," says Spencer, ' k tend to segregate, and the pre-existence of a 
mass of certain units produces, probably by polar attraction, a tendency 
for diffused units of the same kind to aggregate with this mass, rather 
than elsewhere." In the case of the reproduction of a lost part, it must 
be assumed that the organism, as a w r hole, exercises some such power 
over the newly forming part, so as to make it a repetition of its prede- 
cessor. " If a leg is reproduced where there was a leg, and a tail where 
there was a tail, we have no alternative but to conclude, that the aggregate 
forces of the body control the formative processes going on in each 
part." i 

In like manner the mimicry morphological and physiological by 
tumours, of the parts whence they originate, which is always so noticeable, 
may be explained. 

So long as the growing cells are subject to this normal restraining 
influence which has nothing to do with the nerves and bloodvessels, 
themselves integrated structures : they develop in a regular and orderly 
manner, in accordance with the specific hereditary tendency of the 
whole. But when under pathological conditions, this restraining 
influence is modified or withdrawn, then their potential reproductive 
activity may become actual. Cells thus emancipated grow and multiply 
more rapidly than their congeners. This rejuvenescence is the essence of 
the neoplastic process. Hyperplasia and not inflammation is the starting- 
point of every neoplasm. Redundant agamic cell generations are thus 
interpolated in the developmental series, without the concurrence of the 
conditions necessary for their potentialities attaining a physiological 
terminus. 

The developmental outcome of cells thus abnormally set free, depends 
chiefly upon the degree of emancipation attained. In plants and the lower 
animals, such cells tend to form new individuals by agamogenesis ; but, 
in the higher animals, the emancipation is never so complete, and their 
cells are always more or less differentiated ; hence, in these organisms, 
instead of new individuals, only such structural modifications as tumours 

1 This conception seems to me to have far more scientific validity than the alternative 
hypothesis of " tissue tension," etc., adopted by some German pathologists (Weigert, 
Ribbert, etc.). 



138 THE NATURAL HISTORY OF CANCER 

are produced. Under these circumstances, wherever there is a sufficient 
supply of nutritive materials, capable of being utilized for growth by the 
cells of the part, there a neoplasm will arise ; that is to say, the abnormally 
emancipated cells will there grow and multiply more or less independently, 
regardless to the requirements of the adjacent tissues and of the organism 
as a whole. In other words, a new centre of development has arisen. 
Thus the process by which cancers and other neoplasms arise may be 
regarded as a kind of abnormal gemmation, the tumour being the result 
of the modified superinduced repetition of the developmental process ; 
and its qualities, the result of the degree of emancipation of its elements. 
In the case of malignant tumours, cell potentialities of the highest order 
have been awakened ; hence the excessive proliferative activity of their 
constituent cells and their other peculiar features, which together 
constitute malignancy. / 

If we regard the cells combining to form the higher animals as auto- 
nomous beings, 1 possessed of morphological and physiological independ- 
ence, we shall then see although there is no such thing as true alterna- 
tion of generations in the ontogeny of such animals 2 that, nevertheless, 
as Haeckel has pointed out, a very complex alternation of the constituent 
cells does take place, which has a resemblance to it. The developmental 
cycle commences with the union of the male and female reproductive cells, 
>vhence the cytula or fertilized germ results ; which, by agamic multiplica- 
tion,* originates the mass of similar cells called the morula. These 
differentiate into the various cells of the blastodermic layers. By further 
agamic multiplication, the cells of these layers originate the very many 
generations of variously modified cells, whence the different tissues and 
organs arise. All of these polymorphic cell generations multiply agami- 
cally. Eventually, however, two of them differentiate sexually, forming 
the ova and sperm cells. By the union of these, in the act of sexual 
reproduction, the developmental cycle is completed. The reversion of 
the cells has led them back to their original starting-point. 

The only difference between this process and true alternation of 
generation lies in the fact that, in the former, the products of agamo- 
genesis remain in close contact with one another to form a multicellular 
organism ; whereas, in the latter, the agamic products (persons), which 
represent the different generations, are separated and free. But, the 
conditions prevailing in Siphonophora, show that this distinction is not 
of fundamental importance ; for, in these creatures, the same persons 
widely differentiated by division of labour remain united into one stock, 
that in the other hydro-medusae lead separate and independent lives. 
Thus, when the phenomena of gemmation and pathological neoplasia are 
examined in this light, it is obvious that the essential thing in both cases, 
is the interpolation in the developmental series of additional agamic cell 

" All the facts at our command indicate that the tissue-cells possess the same 
morphological organization as the egg-cell or the protozoon ; and the same fundamental 
physiological properties as well," says E. B. Wilson, the ablest exponent of cellular 
biology for English-speaking peoples (1903). 

2 According to Pr. Beard, even in mammalia true alternation of generations does occur, 
the asexual larva being represented by the chorion ; but, at present, this speculation is no 
more than an unproved hypothesis. The conception, however, is of interest ; and, ou 
general a priori grounds, there is much in its favour. 



THE GENESIS OF MALIGNANT TUMOURS 139 

generations, owing to the excess of nutrition in these situations. From 
this standpoint, tumour formation appears as a reversion from dominant 
gamogenesis, to a form of agamogenesis. 

It follows from the foregoing, that the genesis of cancer and other 
tumours, is a phenomenon of the same order as discontinuous growth in 
general. 

Just as cells embedded in the stroma of an ovarium, become ova by 
excessive growth, at the expense of adjacent nutritive materials, which 
they divert from other cells ; so we may infer that those cells which 
originate tumours, become different from their congeners in a similar way. 



Tumour Formation and Developmental Irregularity, with Special 
Reference to the Role of " Rests " in the Origin of Tumours. 

I have previously referred to tumour formation, as being the outcome 
of a futile attempt of certain cells to repeat agamic ally a greater or less 
portion of the ontogenesis. 

In order to elucidate the various types of tumours and their diverse 
qualities from this standpoint, it is necessary to pay particular attention 
to the germs whence they originate ; and to the time at which the process 
starts. 

Cohnheim, who was the first to study this question systematically, 
thought that the germs of all tumours were fragments of the fertilized 
germinal matrix, sequestrated during the earliest period of embryonic 
life. His tumour germs were therefore blastogenic. 1 

The researches of embryologists and teratologists, have shown that 
tumour germs of this kind may really exist. 

Having destroyed one of the first two cells resulting from the initial 
division of the impregnated frog's egg, Roux, Hertwig, Chabry and 
Morgan, found that the other cell, nevertheless, developed into a whole 
embryo of half the normal size ; by shaking the germs of various animals 
and so separating the blastomeres, Driesch, Wilson and others found, 
that each detached blastomere likewise developed into a whole embryo 
of half-size. It has been found that blastomeres isolated at even the 
four-, eight-, or sixteen-cell stages, may sometimes develop into small 
but complete embryos. At later stages, however, detached cells are never 
capable of undergoing such complete developmental exegesis ; for, as 
Driesch and others have shown, when pieces are cut from the evolving 
organism after gastrulation, they do not develop into perfect larvae, but 
only into various defective or monstrous forms. These experiments 
indicate that the power of a single cell to reproduce the entire organism 
is, in the highest animals, limited to the earliest stages of cleavage ; for 
it is only these cells that contain all the elements requisite for complete 
developmental exegesis. 

In the course of his various experiments, Roux often noticed in frog 
embryos with closed medullary canal, isolated blastomeres, belonging to a 

1 Even before Cohnheim's time, Liicke and others had advocated a similar origin for 
teratomata. 



140 THE NATURAL HISTORY OF CANCER 

much earlier developmental stage ; * and these he thought might become 
tumour germs. Beard has met with a similar condition in studying the 
embryology of Raja batis ; while Barfurth, experimenting as to the 
regeneration of the germinal layers, found when these were punctured in 
-xC the gastrula stage, so that cells were displaced and involuted, that these 
heterotopic elements nevertheless continued their growth, in such a 
manner as suggested the probability of their eventually becoming tumour 
germs. 

Wilson, Roux, and others, by shaking and various other mechanical 
devices tending to separate the blastomeres, found that in this way 
homologous twins and various grades of double mounters were frequently 
produced. 

By the implantation of blastoderms of fowl's eggs, embryos, and 
fragments of the same, into the subcutaneous tissues of chicks, Fere 2 
claims to have succeeded in producing teratomatous tumours artificially ; 
and the remarkable result obtained by Nichols, 3 by implanting the entire 
foetus into the subcutaneous tissue of the mother, whence ajbumour very 
like a teratoid was produced, supports Fere's claims. 

It follows from consideration of the foregoing facts, that the only kind 
of tumours likely to arise from Cohnheim's blastogenic germs, are those in 
which the whole ontogenetical cycle is structurally represented ; that is 
to say, the embryomata or teratoid tumours, which may be regarded as 
the very imperfect twin brothers or sisters of the porteur. This kind of 
neoplasm is the type of tumour formation in excelsis. Such tumours 
might with equal propriety be classed with the double monsters by 
inclusion, for they are identical with those formations described by 
teratologists as foetus in fcetu. So far then as these tumours are con- 
cerned, tumour genesis is seen to be akin to teratogenesis developmental 
irregularity being the factor common to both. 

It seen?! not unreasonable to regard the process by which such results 
are attained, as being a kind of reproduction by gemmation ; here, as in 
the lowest organisms, when the growth of the fertilized germ exceeds a 
certain amount, it tends to the formation of one or more new individuals, 
rather than to further enlargement of the original one. 

Cohnheim thought that his blastogenic tumour germs might begin 
their growth into tumours immediately after sequestration, or at any 
subsequent period of the ontogenesis ; or that they might lie dormant in 
the tissues, without ever undergoing any further change. The life- 
history of teratoid tumours seems to warrant this suggestion ; which is 
also in accordance with appearances observed by embryologists. 

It not unfrequently happens that malignant neoplastic changes 
epitheliomatous and sarcomatous supervene in connexion with these 
teratoid formations ; and changes of this kind are no doubt of commoner 
occurrence in them, than in the corresponding parts of normally con- 
stituted beings. This is only what might be expected a priori, considering 



1 R. Owen was one of the first biologists who specially called attention to aberrant 
lin unchanged and become included in the body of 



cells of this kind : " which may remain 
the embryo " ("Parthenogenesis," 1849). 

2 C. R. Soc. de Biologie, 1905 ; also Arch. d'Anat. Micros., 1897-1898. 

3 Third Report Croft Cancer Committee of Harvard Medical School, 1905, p. 120. 



THE GENESIS OF MALIGNANT TUMOURS 141 

the manifold imperfections in their development, and especially their 
undue richness in lowly organized cells still capable of growth and 
development ; and, therefore, endowed with a high degree of proliferative 
potentiality. 

From the genet ical standpoint, tumours may with propriety be 
divided into two classes : (a) the teratoid (blastogenic) ; and (6) the 
histioid (somatogenic). 

It is to the genesis of the latter group of tumours, that we now have 
to direct our attention. 

As I have previously remarked, after gastrulation and the differentia- 
tion of the germinal layers, no cells are ever formed in the higher animals, 
like those of the morula, whence a complete new being may be formed. 
Cells subsequently arising can only develop certain tissue structures, 
viz., those which are normally derived from the germinal layer whence 
they originate ; thus, derivatives of the epiblast always remain within 
this type, and never originate mesoblastic structures, and vice versd. In 
the development of tumours, the same law is observed : there are among 
these formations no transitions from one tissue-type to another. It is * 
necessary to insist on this, because some modern pathologists still uphold A ; 
the ancient doctrine of metaplasia countenanced by Virchow according 
to which, the connective tissue is regarded as an indifferent matrix, 
whence any tissue may arise. This doctrine ignores the specificity of 
the tissue elements, which embryology has revealed ; and it must therefore 
be rejected. 

From the foregoing considerations, it follows that the physiological 
prototype of a histioid tumour, must be something less than an entire 
individual : their prototypes are, in fact, to be found in the various organs 
and tissues of the body, as they are formed after the differentiation of the 
germinal layers, whether in pre- or post-natal life. Thus, the precise 
period of time at which histioid tumours may originate is subject to wide 
variation, and this entails in the resulting neoplasms corresponding 
diversities ; for, as ontogenesis proceeds, there is concomitant differentia- 
tion, first of the cytoplasm of the cells and subsequently of their nuclei, 
whereby progressive loss of reproductive capacity is entailed, so that 
in certain cells it may eventually be impossible to elicit any proliferative 
activity by ordinary stimuli. 

Hence the portion of the ontogenetical cycle mimicked by histioid 
tumours, must necessarily in all cases be less than that compassed by 
their teratoid congeners ; but, between these extremes, all grades of 
intermediate variations occur. 

In the ordinary course of organic evolution, the grqwth and develop- 
ment of the cells proceeds in a regular and ordinary manner, in accordance 
with the specific hereditary tendency of the whole. But the process once 
started, does not cease on account of irregularity, or because it is taking a 
wrong direction. Hence cells may arise at a place where they have no 
business ; or at a time when they ought not to be produced ; or to an 
extent that is at variance with the normal formation of the organism. 

In the earliest stages of ontogenesis, as we have seen, teratoid tumours 
and double monsters are among the consequences of these developmental 



142 THE NATURAL HISTORY OF CANCER 

irregularities ; and, at later periods, the various histioid tumours, in like 
manner result. 

The rudiment of the embryo begins to appear very soon after gastrula- 
tion ; and by the end of the third month of intra-uterine life, the general 
form of the body and its members is well denned. The germs of the 
more complicated forms of " mixed tumour," dermoids, etc., are probably 
caused by developmental disturbances affecting the embryo, during the 
earlier part of this period. As the life-history of these formations shows, 
malignant neoplastic disease may originate from them at any stage of 
their exegesis ; and there a^e good reasons for believing that they are more 
prone to originate such changes, than are their normally evolved tissue 
prototypes. 

Later developmental disturbances, which may even extend to the 
post-natal period, cause less extensive reactions ; confined, for instance, 
to the rudiments of particular organs, parts or to single tissues etc. 

Underlying the above remarks is the assumption, that the germs of 
histioid tumours arise, like those of teratoid tumours, by sequestration 
of fragments of the matrix of the evolving organs, tissues etc., at different 
stages of their exegesis, owing to various forms of more or less local 
developmental irregularity. 

For the moment, let us assume that all histioid tumours arise from 
germs of this kind, which we will call " rests." Of these structures, as 
of their blastogenic congeners, it may be predicated from study of the 
life-history of histioid tumours ; that they may begin to grow into 
tumours forthwith, or at any subsequent period of the developmental 
stage, or that they may remain permanently latent in the tissues. 

In order to further elucidate the role of " rests " in the origin of 
histioid tumours, it will be well to review the evidence bearing on this 
subject, that has accumulated of late ; especially as, in the publications 
of British pathologists, this subject has hitherto been very inadequately 
treated. 

When this theory of tumour genesis was first announced, very few 
facts could be adduced in support of it. No one then believed in the 
possibility of such an amount of developmental irregularity as it pre- 
supposed. The light of modern science has, however, effectually dissi- 
pated this misconception ; and our eyes have been opened to the hidden 
defects of normality. Sequestrated fragments of the various tissues and 
organs have now been found to exist, in every part of the body that has 
been specially examined for them. In short, it is evident that, in the 
course of ontogeny, innumerable fragments of the evolving tissues and 
organs are thrown off ; which, as development proceeds, become embedded 
in the tissues whe-e, as a rule, they remain quiescent. Thus, during 
the last thirty years, pathologists have added a new chapter to human 
morphology ; of which, however, the anatomists as yet seem hardly 
to be aware. It is to belated structures of this kind, that the term 
" rests " is applied. My conception of the significance of this term 
differs somewhat from Cohnheim's. He thought that " rests " consisted 
solely of germ elements ; which, after sequestration, lay dormant in the 
body as embryonic rudiments. As previously mentioned, " rests " of 



THE GENESIS OF MALIGNANT TUMOURS 143 

this kind probably exist, and from them blastogenic tumours arise ; but, 
the " rests " with which histology has made us acquainted, always 
present indications of having undergone more or less developmental 
exegesis, along the lines proper to the parental tissue. 

Long before Cohnheim's time, the proneness of certain congenital 
defects to originate malignant tumours had been recognized by patho- 
logists, especially by Paget, Pemberton, and Virchow. That naevi are 
particularly apt to develop malignant disease, is a very ancient dis- 
covery ; it was, for instance, well known and commented on by Recamier, 
Walther and others, at the beginning of the nineteenth century. Even 
as far back as 1853, referring to the proneness of melanomata to arise 
from pigmented moles, Paget x said : " It seems a striking illustration of 
the weakness in resisting disease, which belongs to parts congenitally 
abnormal." In another passage he adds : " This peculiarity may make 
us suspect that there may be other, though invisible, defects of first 
formation in our organs, which may render them, or even small portions 
of them, peculiarly apt for the seats of malignant and other specific 
diseases." 

In 1858, Pemberton 2 pointed out that of thirty-four cutaneous 
melanomata, studied by him, no less than fifteen obviously arose from 
congenital nsevj. moles, warts, or other local blemishes. 

About the period 1854-1855, Remak 3 having demonstrated the origin 
of " cholesteatomata " from detached, invaginated, epidermoidal 
" rests " ; also showed that the occurrence of malignant epithelial 
tumours, in regions where epithelium is normally non-existent, was the 
result of heterotopia of pre-natal origin. 

Roser, 4 at about the same time, traced the origin of dermoids of the 
neck to sequestration of epidermoidal elements, in connexion with the 
closure of the branchial clefts ; while Verneuil 5 demonstrated, in a very 
conclusive manner, the genetic connexion between scrotal, testicular 
and other dermoids, and somewhat similar local developmental 
irregularities. 

Subsequently Virchow 6 developed the subject still more fully, showing 
that sarcomatous tumours of the skin often originated from ngevi, moles, 
soft warts (verrucas molles), and other congenital anomalies. 

Under these circumstances, it seems unreasonable for the admirers of 
Durante 7 to claim for him the authorship of the " rest " theory of 
tumours, because he published a year or two before Cohnheim's " Vor- 
lesungen " appeared a brochure 8 on : " The Physico-pathological Con- 
nexion between Maternal Nsevi and the Genesis of some Malignant 
Tumours. v Paget and Virchow never advanced such claims, although 
they were far more entitled to do so than Durante. The truth is, for 

Surgical Pathology," 1853, vol. S., p. 490. 

Observations on Pathology, etc., of Cancerous Diseases," part i. (Melanosis), 
185 . 

Deutsche Klinik," 1854, p. 160. 
Handb. d. Anat.-chir.," 1854. 

Mem. sur. 1'inclusion scrotale et testiculaire," 1855. 
Path, des Tumeurs," 1869, t. ii., p. 218 et seq. 
Eyre, British Medical Journal, 1896, vol. ii., p. 1441. 
Archiv. di Palasciano, May, 1874. 



144 THE NATURAL HISTORY OF CANCER 

those acquainted with the works of Paget and Virchow, there was nothing 
new in Durante's publication. The credit of elaborating the indications 
furnished by these pioneers, together with his own observations, into a 
comprehensive theory of tumours, and making the same known to the 
profession in general, undoubtedly belongs to Cohnheim. This concep- 
tion seems to have originated in his mind, through careful study of a case 
of renal myo-sarcoma that came under his observation, in an infant 
sixteen months old. The left lumbar region was occupied by a large cir- 
cumscribed tumour, which had destroyed most of the Sidney by com- 
pression, the remains of this organ otherwise unaltered being adherent 
to it. Within the capsule of the right kidney at its upper end there 
was also a similar rounded tumour, quite distinct from the renal substance. 
Both tumours were sarcomatous, and comprised in their structure striped 
muscle elements. It seemed evident to him, that tumours thus circum- 
stanced could only have arisen from heterotopic elements, detached from 
their normal connexions during early pre-natal life ; hence, other facts 
known to him concurring, he concluded that all tumours thus originated. 



Uterine Tumours and " Rests." 

We have now to study a little more closely the genesis of histioid 
tumours from " rests " ; and, as this is far too large a subject to treat here 
in detail, I must be satisfied with giving a few typical examples. For 
this purpose, I have selected uterine and mammary tumours, as I have 
made a special study of these ; another reason for so doing being, that 
tumours of these organs have hitherto received hardly any attention in 
this connexion. 

Myoma. By far the commonest non-malignant tumour to which 
humanity is prone is the familiar, but little studied, uterine '' fibroid," or 
myoma, whose structure so closely resembles that of the uterine muscu- 
lature, as to suggest the probability of these tumours being little more 
than overgrown fragments thereof, which thorough study of the ensemble 
of the subject emphatically confirms. Moreover, it will be proved that 
the germs whence these tumours arise are sequestrated during pre- 
natal life. The great frequency with which uterine myomata are multiple, 
might of itself lead us to suspect the association of developmental irregu- 
larity with the origin of these tumours ; while the occurrence of cases in 
which the whole musculature is replaced by dense masses of small tumours 
to which I shall subsequently have to refer more in detail specially 
points to this conclusion. 

Although the germs whence most myomata arise are of pre-natal origin, 
it is rare as in the case of such obviously congenital tumours as teratoids 
and dermoids to meet with tumours of this kind during early life : 
Pick ! has, however, described two cases of congenital myoma, in each of 
w r hich the nascent tumour seemed to have caused uterine duplicity, by 
interfering with the blending of the lower segments of the Miillerian 
ducts ; and, in a case reported by Landau, 2 a myomatous tumour 

1 Monats. f. Oeb. u. Gyn., October, 1897. 

2 Berlin, klin. Woch., No. 8, 1901. 



THE GENESIS OF MALIGNANT TUMOURS 145 

obviously of congenital origin occupied the place of the cervix uteri, 
and by compressing the Miillerian ducts in the pre-natal period had caused 
atresia uteri, there being no canalis cervicalis : this tumour contained 
numerous epithelial inclusions, which appeared to be Wolffian residua. 

The fact that uterine myomata often contain various heterotopic 
inclusions comprising epithelial, cartilaginous, calcareous, osseous, 
mucoid, fatty and even rhabdomyomatous elements points to their 
pre-natal origin. 

Recent researches (Rosger, Kleinwachter, Sobotta etc.) have shown 
that the development of the uterine musculature, is closely associated X 
with that of its numerous bloodvessels. The nascent utero-vaginal 
canal, having no proper musculature of its own, is provided with the same 
through the agency of a matrix of mesoblastic cells, which creep round it 
with the evolving bloodvessels. Should (he development of the latter 
be arrested, when this process has already made some progress, the out- 
come might well be just such fragmentation of the musculature, with 
more or less overgrowth of the fragments, as in the specimens described 
in the following case records, which seem to be quite unknown to con- 
temporary gynaecologists : 

1. This patient was under the care of Emmet. 1 When first seen by 
him she was in a very weak and emaciated condition. There was great 
abdominal distension from the tumour, and she suffered much from 
pressure symptoms. Strange to say, there was no metrorrhagia. She 
died of exhaustion soon after Emmet first saw her. 

At the necropsy, the tumour was found to consist of the greatly 
enlarged uterus, converted into a large conglomerate of hundreds of 
myomatous nodules none of great size held together by a thin over- 
lying capsule, through which their inequalities could be seen and felt. On 
section the mass presented the appearance shown in Fig. 6 (next page). The 
division was made with difficulty, as many of the tumours were of dense 
fibrous nature, and others were calcified. The bloodvessels of the part 
were obliterated to such an extent, that only the peripheral nodules pre- 
sented any signs of vascularity. Emmet subsequently met with a second 
case of the same kind. 

2. Meadows 2 has described a similar case as follows : " I have seen 
the uterus completely studded with myomata, both within and without, 
so that on making a section of the uterine wall, the surface looked like 
the skin of a person with small-pox ; so numerous were the tumours that 
it was impossible to count them. They varied in size from a millet-seed 
or less, to that of a small walnut." 

3. Cruveilhier 3 has encountered the like condition. In his case the 
whole musculature was replaced by a multitude of small tumours of this 
kind, most of which were very minute, the largest being no bigger than a 
walnut. Many of the tumours were calcified. The affected uterus pre- 
sented as an irregularly bossed mass, not unlike an ovarian cystoma to 
look at. Some of the tumours projected externally and others internally, 
but most of them were embedded in the musculature. 



_., g j, 1880, p. 525. 2 Gynaecology . 

3 " Anatomic Pathologique," t. ii., liv. xxiv., p. 6. 

10 



146 THE NATURAL HISTORY OF CANCER 

Bland-Sutton * and Haultain 2 have also met with this condition, 
which each of them regarded as " unique," being unaware of the very 
explicit account of this malady in my book on " Uterine Tumours." 

Instead of involving the whole organ, multiple myomata are sometimes 
limited to a special part. In the Hunterian Museum, 3 is a uterus with 
numerous tumours of this kind, which occupy every part of it, except the 
cervix and portio, which are free. Rabenau 4 has met with similar tumours 
limited to the cervix and portio. Stone 5 has described a multinodular 
tumour of the corpus, which consisted of an immense number of small 
growths of vsfcrious shapes. 

If we conceive this process, as restricted to a still narrower area to a 




FIG. 6. MULTIPLE MYOMATA INVOLVING THE WHOLE UTEEDS (EMMET). 
The white areas represent calcified tumours. 

few vascular branches, or even to a single one it is easy to understand 
how the germs of ordinary myomata arise. Thus, these cases are of 
great importance, for enabling us to understand the pathogenesis of 
myomata. 

In some instances, these abnormally evolving myomatous elements 
are intimately connected with " rests " of Wolffian or Miillerian struc- 
tures, or even of the uterine mucosa itself. The discovery of epithelial 
inclusions in uterine myomata, was one of the earliest indications of the 

1 British Medical Journal, 1901, vol. i., p. 814. 

2 Transactions of the Edinburgh Obstetrical Society, 1905, vol. xxx., p. 112. 

3 No. 4,627, Pathological Series. 

4 Berlin, klin. Woch., 1882, vol. xix., p. 170. 

5 American Journal of Obstetrics, etc., October, 1899, p. 519. 



THE GENESIS OF MALIGNANT TUMOURS 147 

correctness of this interpretation. The presence of these foreign elements 
was first demonstrated by Babes, 1 and Diesterweg, 2 in 1882 ; and their 
observations have since been confirmed and amplified by Shottlander, 
Hauser, Ricker, Orloff, Recklinghausen, Meyer, Hirst, and others. They 
present either as solid cellular aggregations of various shapes and sizes, or 
as tubules, cysts, or structures not unlike utricular glands ; in any case, 
the peripheral cells are of more or less columnar or cubical shape, and 
they may be ciliated. Many observers (Meyer, Tourneux, Ricker, Fischel, 
Coblenz etc.) have found similar epithelial inclusions from which they 
believe certain cysts arise in the otherwise normal uterine musculature. 

By Babes and Recklinghausen these structures are believed to be 
Wolffian relics, while other pathologists insist on their Miillerian origin. 
But all such bodies are not necessarily either Wolffian or Miillerian 
residua, 3 for they may be included sequestra from the uterine mucosa 
itself. Indeed, Ribbert has found deep in the uterine wall not only 
sequestrated utricular glands, but even isolated fragments of the entire 
mucosa. In this connexion it is worth noting that, according to 
R. Meyer, 4 glandular structures are found in the mucosa, even as early as 
the seventh month of foetal life, and they often penetrated deeply and 
were even aberrant ; but this pre-natal origin for the uterine mucosal 
glands is, of course, contrary to the usually received opinion, according 
to which these structures are entirely of post-natal origin. In the face of 
Meyer's results, however, this opinion can no longer be maintained. 

Heterotopic epithelial elements, are not present in all myomata, and 
the exact proportion of cases in which they occur has yet to be deter- 
mined ; the careful researches of Orloff, who examined serial sections of 
fifty-five specimens of small myomata, revealed only four instances of 
epithelial inclusions. 

The researches of Coblenz, Meyer, Recklinghausen and others, have 
shown that the track of the utero- vaginal canal is strewn with epithelial 
debris, chiefly of Wolffian origin ; hence, it is not surprising, in the process 
of building up the musculature, and in the coming together of the various 
ducts from the fusion of which the uterus and vagina result, that these 
aberrant epithelial elements are sometimes included in myomatous 
sequestrations ; and no doubt the migrations and changed relations of 
the parts incidental to ontogeny, as well as the correlations between the 
musculature and its numerous bloodvessels, which are so extraordinarily 
interwoven, are also favouring factors. Such is the manner in which I 
believe the germs of myomata originate. 

Some of those who have specially studied the subject, believe that 
germs of this kind also arise, by a similar process, during post-natal life ; 
but, if this really be so, it has yet to be proved. So far as I can judge, 
the general drift of the ensemble of the evidence now available, is decidedly 

1 Allgem. Wien. med. Zeitung, 1882, Nos. 36 and 48. 

2 Zeits. f. Oeb. u. Gyn., 1883, vol. ix., p. 191. 

3 Evelt (Munch, med. Woch., August 18, 1903) having reported an instance of 
melanotic malignant tumour, as primarily arising from a corpus myoma, this raises the 
question of ectodermal inclusions in such tumours ; and, on the hypothesis of ectodermal 
" rests," other instances of primary uterine melanoma may thus be accounted for. 

* " Ueber epitheliale Gebilde im Myometrium des f cetalen und kindlichen Uterus " etc. 
Berlin, 1902. 

102 



148 THE NATURAL HISTORY OF CANCER 

^- against this hypothesis : the germs of myomata always appear to be of 
/ pre-natal origin. 

In this connexion it is well to remember, thafc myomata are not 
confined to the uterus and its vicinity, although they are of much more 
frequent occurrence here than elsewhere. Like their uterine congeners, 
the extra-uterine myomata are often multiple ; and they not infrequently 
contain epithelial and more rarely other inclusions. 

If the foregoing views as to the origin of myomata be correct, it follows 
that extrinsic factors, such as local irritation and chronic inflammation 
whether due to traumata, microbes, or other external irritants play 
but a secondary part in their causation. 

In concluding this subject, I have only to remark that malignant 
disease sometimes but rarely originates from myomatous tumours ; 
but of this more anon. 

Lipoma. Although fatty tissue is not normally present in the uterus, 
yet, as I have before mentioned, it is sometimes found included in myo- 
mata (T. Smith, Jacobson, Briinings, Seydel) ; moreover, instances of 
fatty tumours in the uterus have been reported (Knox, Stroinski, Busch, 
Orth, A. G. Ellis, Merkel [two cases], and Seeger). The only rational 
explanation of these heterotopic formations is sequestration, with dis- 
placement of fatty tissue matrix during the pre-natal period. Fatty 
tumours have also been found in the vicinity of the uterus e.g., in the 
broad ligaments (Treves, Prenice, Terrilon), round ligaments (Witte), 
recto-vaginal septum (S. Wells, Pelletan), tube (Parona), recto-uterine 
cul-de-sac (Laffore) etc. ; where they are just as heterotopic as in the 
uterus itself. 

Osteoma and Chondroma. The circumstances under which cartila- 
ginous and osseous structures are met with in the uterus, are similar to 
those which condition the occurrence of fatty tissue in this organ, where 
such structures are always heterotopic. In the cervix of an otherwise 
normal foetal uterus, R. Meyer * found a bony nodule, closely associated 
with a vestige of the Wolffian duct, through the medium of which it had 
evidently been introduced ab extra (Fig. 7). In this connexion, it is of 
interest to note that bone- and cartilage-containing tumours arise more 
frequently from this part of the uterus than elsewhere. This is specially 
obvious with regard to the peculiar forms of "mixed" sarcomata, to which 
this part is prone, whose structure comprises such various heterotopic 
structures, as cartilage, bone, striped muscle, fat, mucous tissue, epithelial 
elements etc., of which so many instances have been reported ; and I 
think there can be no doubt, that the germs of these tumours are aberrant 
elements sequestrated from the matrix of adjacent tissues during early 
pre-natal life. I have cited many examples of this kind, in my books on 
Uterine and on Vaginal Tumours. Gebhard has met with a malig- 
nant epithelial growth of this vicinity, whose stroma was studded with 
bits of hyaline cartilage. If malignant tumours of this locality were 
carefully examined, in serial sections, ad hoc, it would probably be found 
that aberrant elements of this kind are not particularly rare. 

1 "Knocheoherd in der Cervix eines foetalen Uterus," Arch. f. path. Anat., 1902. 
Bd. clxvii., S. 81. 



THE GENESIS OF MALIGNANT TUMOURS 149 

Even as long ago as 1849, Lebert had in two specimens demon- 
strated the presence of true bone in uterine myomata ; and, at about the 
same period, J. H. Bennet found cartilage ; similar finds have since been 
made by Henle, Bidder, Freund, Ascher, Feuchtwanger, Johnston, and 
others ; so that the occurrence of this kind of heterotopia is established 
beyond cavil. The only possible scientific explanation of such conditions, 
is the inclusion of osteo- and chondro-blasts in the nascent myomata, by 
sequestration from adjacent parts during early foetal life. 

In like manner, the remarkable proneness of uterine myomata to 
fibrification and calcification, probably depends upon the inclusion of 




FIG. 7. A NODULE OF BONE IN THE CERVIX OF AN OTHERWISE NORMAL F<ETAL 
UTERUS (R. MEYER). 



Transverse Section of the Pelvic Organs under a low magnifying power. 

t's pouch ; U, uterus ; K, nodule of boi 
obliterated Wolffian duct ; V, bladder. 



R, Rectum ; D, Douglas's pouch ; U, uterus ; K, nodule of bone in the vicinity of the 

"blite 



heterotopic fibrinogenous and sclerogenous elements ab extra ; for such 
proclivities are foreign to the normal uterine musculature. 

The occurrence of osseous and chondromatous tumours in the uterus 
of which instances have been reported by Miller, Seydel etc. can only 
be interpreted on similar lines. In Miller's case, an osseous tumour 
occupied the site of the corpus of a malformed uterus, the patient being 
a girl, sixteen years old, in whom the vagina was absent. 

Here it should be noted, that osseous and cartilaginous structures are 
also sometimes met with in sarcomatous tumours of the uterus, other 
than those peculiar forms above referred to, of which instances are given 
in my book on " Uterine Tumours." 



150 THE NATURAL HISTORY OF CANCER 

Bone and cartilage-containing tumours have also been met with in 
the vicinity of the uterus, e.g., in the ovary (Baet, Barnes, Donati, etc.), 
in the broad ligament (Kaul-chondrifying sarcoma), and in the recto- 
uterine cul-de-sac (Hugenberger). 

Cysts. Very interesting in this connexion is the little-studied subject 
of cyst-genesis in the uterus ; for, nearly all formations of this kind un- 
doubtedly arise, as the outcome of pre-natal developmental irregularity. 

The discovery of aberrant epithelial inclusions of various kinds in the 
uterine wall and its vicinity, to which I have previously referred, enables 
us to understand the sources whence many uterine cysts arise. These 
heterotopic elements have been described by various authors as of Wolffian, 
Miillerian and mucosal origin ; and probably all these sources are repre- 
sented in the germs of uterine cysts. As many recent researches have 
shown, the track of the uro-genital anlage is strewn with debris of this 
kind. 

The commonest uterine cysts undoubtedly are the small multiple ones 
of the cervix and its vicinity, which only occasionaUy increase to such a 
size as to merit the name of disease. The histological structure of these 
cysts, as well as the peculiar nature of their fluid contents, enable us to 
recognize their identity with the glands of the cervix, of which they are 
obviously sequestrations. The well-known ovula Nabothii are the 
prototypes of these cysts, which R. Meyer has discriminated in the pre- 
natal period. 

In the antero-lateral part of the cervix and the adjacent parts of the 
uterus, cysts are occasionally found lined by a single layer of cubical 
epithelium quite different from that of the glands of the cervix which, 
it appears certain, are derived from the cystic distension of unobliterated 
portions of the Wolffian duct (Gartner's), such as Meyer, Nagel, Tourneux, 
Rieder, and others, have discovered in this vicinity. In pre-natal life. 
Meyer found that these vestigial remains were more extensive, and of more 
frequent occurrence, than after birth. Cysts of this kind some of them 
congenital have been studied by Burckhardt, Senn, Klein, Rieder and 
many others. 

* We are indebted to the admirable researches of Coblenz, 1 the signifi- 
cance of which are even now T not fully appreciated, for recognition of the 
fact that papilliferous cysts may develop anywhere along the course of the 
Wolffian (Gartner's) ducts ; and he has also shown that the germs whence 
these cysts arise are Wolffian residua derivatives of the paroophoron, 
or, as is rarer, of the epoophoron. The work of Recklinghausen, Meyer, 
Pick, Landau and others, confirms and extends Coblenz' results. 

Residua of this kind have been detected in the otherwise normal 
uterine musculature by Coblenz, Ricker, Rieder, Meyer, and others ; 
and, in the adjacent structures e.g., broad ligament, round ligament, 
pelvic connective tissue, tube, ovary etc. 

As examples of cystic tumours arising in the uterine walls from these 
Wolffian residua, reference may be made to Czerwenka's case of <; cyst- 
adenoma papillare proliferans " ; to Gusserow's case of " cystic adenoma " ; 
to Ahlf eld's case of " kystoma multiloculare " of the cervix and portio 
1 Arch. f. path. Anat., 1881, Bd. Ixxxiv., S. 26. 



THE GENESIS OF MALIGNANT TUMOURS 151 

etc., as well as to older cases of like nature reported by Cruveilhier, Lebert 
and Rokitansky. Meyer has met with a large congenital tumour of this 
type, in an eight-month foetus, which had evolved in close proximity to 
Gartner's duct. 

A congenital polycystic condition of the corpus uteri, with cystic 
adeno-myoma of the cervix, has been described by Woskresensky ; and 
Mears 1 has reported a remarkable case in which congenital polycystic 
changes affected the uterus, ovaries, and kidneys simultaneously, as if 
owing to some developmental irregularity affecting the evolution of the 
whole Wolffian body. 

Similar cystic papilliferous tumours have been met with in the vagina, 
in the para-uterine and para-vaginal connective tissue, in the broad 
ligaments, round ligaments etc. 

Here also mention may be made of the fact, that in nearly all of the 
above-mentioned localities myomatous tumours, comprising well-marked 
Wolffian residua the so-called " mesonephric myomata " have lately 
been discriminated. 

Since these papilliferous and other cystic tumours are identical in 
structure with the ordinary forms of ovarian cystoma, the important 
inference may be drawn, that these ovarian cysts also arise from included 
Wolffian residua ; as to which it seems to me the cumulative evidence 
from various sources is so strong, as to be practically conclusive. And 
in the same category, I doubt not, congenital polycystic disease of the 
kidneys should be included. It would require more space than is here 
available to fully prove this thesis ; but I have at hand all the evidence 
for doing so. As an indication of the correctness of this interpretation, 
reference may here be made to the obvious correspondence between the 
different forms of ovarian and broad-ligament cysts, which holds good 
even for dermoids. 

Dermoids. The researches of Sanger have made it perfectly clear, 
that dermoids do originate in the pelvic connective tissue and adjacent 
structures, quite independently of the ovaries. Thus, formations of this 
kind have been found in the pelvic connective tissue (Hofer, Germain, 
Sanger) ; between the vagina and rectum (Mahomed, Mannel, Merriman) ; 
between the cervix uteri and rectum (Emmet, Cartez, Barette, Beyea) ; 
between the bladder and uterus (Kiister, Sanger, Charcot) ; in the urethro- 
vaginal septum (Englisch, Wiggin) ; in the tube (Pozzi, Treub, Ritchie, 
Orthmann) ; in the broad ligaments (Abel, Marshall, Lunn, Gottschalk, 
Rendu, Hofer etc.) ; in the round ligament (Rendu) ; in the vagina 
(Watts, Veit) ; while in the bladder and rectum many such cases have been 
reported. 

In several of the sites of these pelvic dermoids, ectodermal " rests " 
have been detected in foetal or early post-natal life ; e.g., in the broad 
ligaments by Meyer, Switalski, Ribbert (Fig. 8, next page), and March- 
and ; in the pelvic connective tissue (especially in and in the vicinity of 
the lymph-glands) by Wakefield ; in the musculature at the neck of the 
bladder by Meyer etc. 

I am not aware that extrinsic ectodermal elements of this kind, have 
1 Philadelphia Medical Times, U.S., 1872, p. 314. 



152 



THE NATURAL HISTORY OF CANCER 



hitherto ever been detected in the otherwise normal uterine parenchyma ; 
but it is, nevertheless, tolerably certain, if the cervix were systematically 
examined ad hoc, that such would be found. The presence of epidermoidal 
elements in certain sarcomata of the lower part of the uterus, as in 
cases described by Hauser, Rosenstein etc., points to this conclusion ; 
and of like significance is the occurrence of melanotic elements in sarcomata 
of this part, as described by Whitridge Williams, Johnston etc., and in a 
uterine myoma by Evelt. 

Very little is to be found in pathological publications, as to uterine 
dermoids ; indeed, until Sanger (1890) had made it perfectly clear that 
these formations do originate in the pelvic connective tissue, quite inde- 




FIG. 8. A HETBKOTOPIC, HORNIFYING, EPIDERMOIDAL "REST" IN THE BROAD 
LIGAMENT (RIBBERT). 

E, The aberrant epidermoidal nodule ; B, Connective tissue of the broad ligament ; 
O, ovary ; W, W, Wolffian tubules. 

pendently of the ovaries, the possibility of such occurrences was generally 
disbelieved. With such facts as those above cited before us, it would, 
however, now be unreasonable to maintain such a sceptical attitude. 
In comparatively recent times, examples of the simplest form of uterine 
dermoid cyst, with sebaceous or cholesteatomatous contents, have been 
studied by Ahlfeld, Cornil, Allen, French, Recklinghausen, and Shoe- 
maker ; in the older publications, examples of somewhat more complicated 
forms (piliferous) are recorded by Vicq d'Azyr and Fabricius Hildanus ; 
and, in recent times, teeth and hairs, as in Stewart's case ; while, a few 
years ago, a still more complicated tumour of this kind was described by 
Geyl i 1 this formation was connected with the posterior part of the vaginal 
fornix, and besides skin, it comprised such diverse structures as bone, 
striped muscle, fat, nerve etc. 

At an early stage of pre-natal development, the Wolffian duct is in 
1 SammL. klin. Vortrage, N.F., No. 190, 1897. 



THE GENESIS OF MALIGNANT TUMOURS 153 

such close proximity to the ectoderm, that many embryologists now 
maintain its ectodermal origin. However this may be, it is certain that 
in its subsequent migration, this duct may carry away with it ectodermal 
elements, which may thus be lodged in the uterus, pelvic connective 
tissue, ovary or other pelvic organs, where dermoid cysts have been found. 
It is to foreign elements thus imported during early pre-natal life, that 
we must ascribe the germs of these various dermoid tumours. 

Ovarian and other dermoids are known to have marked proclivity 
to originate malignant disease, but hitherto no instance of this kind 
has been reported in connexion with these pelvic dermoids, unless an old 
case by J. S. Bedford : -; Sarcomatous Tumour of the Uterus containing 
Hairs and Stearine," is of this nature ; but several examples of primary v / 
malignant epithelial and connective-tissue tumours of the pelvic areolar 
tissue, obviously of heterotopic origin, have been met with (Heinsius, 
Herff, W. M. Smith and Kaul chondro-sarcoma). 

The probable origin of certain uterine and vaginal tumours from 
" rests " of the Miillerian ducts, that have failed to fuse and blend in the 
formation of the utero-vaginal canal, was first suggested by Freund. 
He described myomatous cystic tumours of this kind, as occurring in the 
lower part of the uterus and the upper part of the vagina, especially 
posteriorly. 

Similar formations have been met with in the para-uterine con- 
nective tissue (Verneuil, Haussmann). A single layer of columnar 
epithelium, which is often ciliated and may present involutions and 
cysts, lines the interior of these tumours. There are generally traces 
of concomitant uterine duplicity, e.g., uterus bicornis septus etc. In- 
stances of congenital tumours of this kind have been reported by Briesky, 
and others. 

Myomatous uterine tumours, having in their interior diverticula 
communicating with the uterine cavity, as in cases of uterus accessorius 
bifid, trifid uterus etc. have also been reported (Brens, Neugebauer, 
Ricker, Recklinghauseh, Meyer, Hollander, Skene, Delpage and others). 
Such conditions appear to be due to abnormal myomatous growth, 
around persistent diverticula from the Miillerian ducts of pre-natal 
origin. Tumours of this kind are, however, far from common; and* it 
seems to me improbable from consideration of the ensemble of the subject, 
that the ordinary myomata arise from Miillerian " rests." In this con- 
nexion it should be borne in mind, that the Miillerian ducts have no proper 
musculature of their own, the elements whence this is derived being 
superimposed ab extra. 

Another form of uterine cyst, of which many examples have been 
recorded (Leopold, Fehling etc.), is the endothelial-lined formation, 
which is generally believed to be of lymph- angiectasic or telangiectasic 
origin. It is well, however, to recollect that Meyer specially noted the 
frequent invagination and inclusion of small peritoneal pouches, into the 
nascent uterine wall during pre-natal life ; and it is probable that these 
inclusions are the germs whence most cysts of this kind originate. It 
accords with this mode of origin, that Hahnsseau has lately reported 
instances of this variety of cyst, caused by the traumatic inclusion o 



154 THE NATURAL HISTORY OP CANCER 

peritoneum in wounds made during operations on the uterus and its 
adnexa. 

Sarcoma. In the foregoing dissertation, I have proved that the 
germs of all non-malignant uterine tumours are the outcome of develop- 
mental irregularity, during pre-natal life. Did time and space permit, I 
could adduce equally conclusive proof, that the anlagen of all non- 
malignant tumours wherever arising are similarly conditioned. 

This being so, an a priori assumption is inevitably raised, that the 
germs of malignant tumours may also be similarly conditioned. Hence 
we now have to focus our attention on this aspect of the subject, so far 
at least as malignant tumours of the uterus are concerned. 

I have already had occasion to indicate several instances in which the 
heterotopic findings, revealed by histological analysis of tumours of this 
kind together with other facts of like import pointed clearly to pre- 
natal origin ; and most of these tumours were sarcomatous. 

Taken as a whole, a surprisingly large proportion of uterine sarcomata 
are found, on careful examination, to bear the impress of the pre-natal 
stamp. 

Practically all of the important group of " infantile " sarcomata 1 
whether of the lower part of the uterus or of the vagina must be 
included in this category. These tumours are often congenital, or they 
occur very early in life ; they are frequently multiple db initio, and 
accompanied by multiple" polypi ; while other adjacent organs, besides 
the one primarily involved, may be concurrently affected. Their 
structure commonly comprises various heterotopic elements, such as 
striped muscle cells, epithelial islets, leiomyomatous cells and myomatous 
tissue. These various indications point conclusively to their origin from 
pre-natal developmental irregularities ; and it should be noted that of 
the parts apt to be involved, all are more or less concerned in the for- , 
mation of the cloaca ; indeed, it is with the formation of this structure 
even more than with that of the uterus that the germs of this curious 
disease originate by sequestration and inclusion, during the various 
processes of approximation and fusion of the constituent parts involved 
therein. 

'Another considerable group of uterine sarcomata, which recent 
research has shown to be much less rare than was formerly believed, is 
the grape-like or botryoidal variety of adults ; which is with few excep- 
tions a malady of the lower part of the uterus. In this, as in some 
other respects, the malady resembles the infantile variety ; but, unlike 
the latter, initial multiplicity especiaUy in adjacent organs such as the 
vagina, bladder and rectum is hardly ever seen. Hence it may be 
inferred that the developmental irregularity concerned in its genesis, 
appertains to the cervix proper rather than to the cloaca. With this 
reservation, the difference in age incidence, and also the different nature 
of the concomitant heterotopic inclusions, e.g., cartilage and bone, 
these two forms of disease have much in common. 

The structure of this peculiar type of sarcoma commonly comprises 

1 For details of illustrative cases the reader is referred to my publications on " Uterine 
Tumours," p. 322, and on " Vaginal Tumours," p. 25. 



THE GENESIS OF MALIGNANT TUMOURS 155 

such various heterotopic constituents as striped muscle, cartilage, bone, 
various types of epithelial elements, mucous tissue etc. ; which, it may 
be inferred, from what I have previously mentioned as to the develop- 
mental anomalies of this part, arise from aberrant elements sequestrated 
from the matrix of adjacent tissues during pre-natal life, and included 
in the nascent organ, probably through the agency of the Wolffian duct 
in most cases. 

Judged by the results of their histological analysis and general mor- 
phology, the remaining uterine sarcomata may be regarded as derivatives 
of the mucosa, or of the parenchyma of the uterine wall. As to the pre- 
natal origin of the germs of these mucosal tumours, we have only a few 
but significant indications ; e.g., Wagner, Geissler and Reid have found 
chondromatous structures in them ; Whitridge Williams, Johnston, 
Taylor, Rokitansky and others, melanotic elements, which can only be 
accounted for as ectodermal inclusions. As to the occasional association 
of tumours of this kind with various gross uterine malformations, I shall 
have to refer to it in the sequel. With regard to the sarcomata of 
parenchymatous origin, some of these undoubtedly arise from myomata 
which, as we have seen, are of pre-natal origin ; and, in this connexion, 
we must not forget Evelt's case of malignant melanoma primarily arising 
in a myoma, to which reference has previously been made. Moreover, 
in these tumours cartilaginous and epithelial " rests " are occasionally 
found, which could only have originated during pre-natal life. It is to 
this latter source, that we must refer the germs of the various remarkable 
cystic sarcomata of parenchymatous origin ; thus, in a case by Aslanian, 
a large multilocular, telangiectasic cysto-sarcoma of this kind, was 
concomitant with abnormal persistence of the Wolffian body ; while 
Coblenz has seen sarcoma of the uterine parenchyma concomitant with a 
unilocular papillary cyst of the right ovary, and multilocular cystic 
disease of the left ovary. 

Of like import are the cases of mixed malignant tumours forms in 
which epitheliomatous and sarcomatous processes go on simultaneously 
of which instances have been reported in the uterus by H. K. Spencer, 
Maier, Kuhnart etc. 

Taking all these various indications into consideration, it seems to 
me impossible to avoid the conclusion, that the germs of all uterine 
sarcomata are probably the outcome of developmental irregularity of 
pre-natal origin. 

Malignant Epithelial Tumours. From what has been previously stated. 
it will be gathered that histioid tumours are never of such a monstrous 
nature, as not to present some analogy to the pre-existing structure 
of the parts whence they originate, either in their pre- or post-natal 
states ; and this holds also for malignant epithelial tumours, as I shall now 
proceed to show. Moreover, it is not only the constituent cells of these 
tumours, wherein the essence of the disease resides, that manifest this 
similitude ; but also the connective-tissue stroma or framework, wherein 
they are set. Thus may be explained the great structural diversities, 
that obtain between the malignant epithelial tumours of different parts, 
and of different tissues, according to the sites whence they originate, 



156 THE NATURAL HISTORY OF CANCER 

which is such a marked feature of all tumours of this kind. What, for 
instance, can be more divergent in this respect, than the appearances 
presented on microscopical examination by sections of cancers from 
such different parts as the breast, the rectum and the skin ? We learn 
from such studies, that malignant epithelial new formations always 
present unmistakable histological resemblance to the structures whence 
they originate. And this resemblance can also be traced in the physio- 
logical properties of their constituent cells ; for, as Waring x has demon- 
strated, the cells of cancer of the stomach and pancreas produce the 
same ferments pepsin, trypsin, etc. as the normal secretory cells of 
these organs. 2 In like manner, Johannes Miiller, more than half a century 
ago, proved the presence of casein in cancers of the female breast ; and 
the abundance of fatty matters contained in the cells of these neoplasms 
is well known. We are thus reminded of the similar metamorphoses that 
the cells of the normal gland undergo during lactation ; but, the nearest 
approach to normal secretion, that the tumour structure ever produces is 
a scanty mucoid fluid, presenting some resemblance to a poor kind of 
colostrum. Such a result is quite in accordance with the experiments of 
Martinotti, which show that the cells of secretory glands when in a state 
of active growth and proliferation, tend to lose their normal secretory 
aptitudes there being a certain antagonism between proliferative and 
secretory changes. 

Similarly, cancers of the cervix uteri may be expected to yield indica- 
tions of the presence of substances identical with the cervical mucus ; 
and, in this respect, they will probably be found to differ from cancers 
of the corpus. As tending to confirm this expectation, it may be men- 
tioned that Cornil and others have observed, in the constituent cells of 
cervical cancers, indications of mucoid or calyciform changes, similar to 
those that are so characteristic of the epithelium of the cervical glands 
during the elaboration of their peculiar secretion. 

The cornifying properties of epidermoidal cancers of the skin, likewise 
exemplify the same peculiarity. 

The characteristics of the stroma of cancerous tumours, are chiefly 
determined by the pre-existing structure of the affected part. Its 
alveolar disposition, which was formerly regarded as the histological 
criterion of cancer, is now known to be merely a local peculiarity. 

In its minute structure and general characters, the stroma of 
mammary cancer closely resembles the stroma of the normal gland, of 
which it is evidently a derivative. It consists of thick bands of dense 
white fibrous tissue, containing elastic fibres and anastomosing con- 
nective-tissue cells, which are specially numerous at the meeting-points 
of the diverging bands. The characteristic hardness of mammary 
cancer is mainly due to its abundance and density ; in fact, hard cancers 
are the dominant forms that arise from regions rich in fibrous tissue. 
Moreover, it is noticeable that elastic fibres are met with in great abund- 
ance in cancers that arise from structures normally rich in them, such 

1 Journal of Anatomy, October, 1893, p. 142. 

2 In pancreatic cancers, besides trypsin, Waring found amylopsin, steapsiu, and a 
milk-curdling ferment. 



THE GENESIS OF MALIGNANT TUMOURS 157 

as the breast and skin. Miiller attributes the large amount of gelatin 
found on analysis in mammary cancers, to the abundance of its fibrous 
stroma. 

On the other hand, the stroma of uterine cancers consists of scanty 
fibrillar tissue, like that met with in the normal uterine mucosa, which it 
further resembles in that it usually contains unstriped muscle cells. 
Hence little or no gelatin is found in uterine cancers. 

Another marked characteristic of cancerous tumours that must be 
mentioned here, is the great resemblance always noticeable between the 
primary and secondary growths, the significance of which it is impossible 
to ignore. As Moxon has sagely remarked : " The first cancer which 
appears has a likeness to the part in which it appears, and the secondary 
cancers arising from it have the likeness of that first cancer ; and those 
who doubt that they come from that first cancer must show us why 
they have that likeness." In this connexion Waring's observations are 
of great interest, for they show that the same physiological properties 
are manifested by the cells of the secondary, as by those of the primary 
growths. In short, the secondary growths repeat the distinctive 
characters of the primary growth with such fidelity, that the seat of the 
latter may often be correctly surmised by careful examination of the 
former. 

Bearing in mind these considerations and what they imply, we are 
now in a position to come to closer quarters with the question of the 
genesis of uterine cancer. 

Insuperable difficulties surround the investigation of the very earliest 
stages of primary cancer formation ; but, in the formation of secondary 
cancers, nature is constantly performing the miracle of cancer genesis 
under our very eyes, and in a manner that admits of scientific investiga- 
tion. There are good reasons for believing that primary cancers arise, 
exactly as do these secondary formations ; so that, by investigating the 
latter, we may be able to elucidate the former. 

Now, the most important fact revealed by the study of the origin of 
secondary cancer is, that the germ whence it arises which must be very 
small is not a normal constituent of the affected part, but an intruder 
ab extra. Can the like be said of the germ of primary cancer ? The 
histological analysis of primary cancers of the uterus shows that the 
majority of these tumours consist of structures, which have remarkable 
similitude to those normally comprised in the mucosa of the part ; and 
from this it follows, that the germs of these tumours must be derivatives 
of this structure whether of pre- or post-natal origin. 

Thus, the only kind of heterotopia that can be admitted for the germs 
of these uterine cancers, is a local heterotopia, referable to developmental 
irregularity of the mucosa itself. In this restricted sense, as I shall 
proceed to show, the germs of most uterine cancers are decidedly 
heterotopic, that is to say, they are not direct derivatives of the normally 
integrated, pre-existing cells of the part. 

The great majority of uterine cancers arise in the cervix ; and, among 
these tumours, it is not uncommon to meet with forms, which, on histo- 
logical examination, present no recognizable similitude either to the 



158 THE NATURAL HISTORY OF CAXCER 

glandular or to the epidermoidal structures of the cervical mucosa. The 
germs of some of these tumours may be as truly heterotopic, as those of 
the secondary cancers ; that is to say, they may be derived from ecto- 
dermal elements sequestrated during early pre-natal life r and included in 
the nascent uterus with the Wolffian duct ; or, it is even conceivable, 
that they may be " rests " of this latter structure. We know that 
tumours of this kind and thus derived, do form in parts adjacent to the 
uterus, such as the pe.vic connective tissue etc. ; and, therefore, it 
seems not unreasonable to infer that they may also originate thus in the 
uterus itself. It may even be surmised, that the undue proclivity of 
this part of the uterus to malignant epithelial tumours, is explicable in 
this way. 

However this may be, the fact remains that the histological elements 
of most uterine cancers so closely resemble those normally met with in 
the uterine mucosa, that we may classify them as being either of the 
cylinder-celled or epidermoidal type, v 

The mucosa of the uterine cavity is lined throughout by a single layer 
of cylinder-shaped epithelial cells ; and the innumerable glands which 
open on its surface, are the result of follicular depressions of this epithelial 
lining into the sub-mucosa. In the midst of this cylinder-celled epithelial 
lining of the corpus uteri, small islets of aberrant epidermoidal cells, 
have often been detected (Ries, Zeller, Schuchardt, Fritsch, Friedlander 
etc.); and probably this condition is fairly common. Once this fact has 
been grasped, there can be no difficulty in recognizing these heterotopic 
elements, as the germs of those hornifying epidermoidal cancers of this 
part, of which examples have been reported by Gellhorn, Ries, Piering, 
Gebhard, Keith, Flaischlen, Lohlein, Emanuel, Kaufmann and others. In 
several instances of initial multiplicity, epidermoidal cancer has been 
found coexistent with cylinder-celled cancer of the same uterus (Hofmeier, 
Winter, Schauta etc.) ; and some cases have been reported, in which the 
two kinds of epithelium were associated in the same tumour (Hirschmann). 

The mucosa of the cervix, as to its upper two-thirds, is lined by a 
single layer of cylindrical epithelial cells ; whereas, a laminated, flattened, 
epidermoidal type of epithelium which is an upward extension of that 
covering the portio lines more or less of its lower part ; at least, this is 
the usual condition in multiparse, in whom the flattened cells of the 
portio are prolonged for a variable often considerable distance, within 
the canalis cervicalis. It is probable that the heterotopic epidermoidal 
cells found in the mucosa of the corpus, are detached aberrant offsets 
from these upward extensions of the portio cells, sequestrated during 
pre-natal life. It accords with this, that ViUiers and Therese have 
demonstrated, in the midst of the cylinder- celled lining of the cervical 
mucosa, detached islets of epidermoidal cells, with Malpighian stratum 
etc., where they presented as whitish plaques. Such no doubt are the 
germs, whence the considerable number of epidermoidal-celled cancers 
of this part of the cervix arise. 

In its structure, the lining membrane of the portio differs from that 
of the rest of the uterus, resembling rather that of the vagina. Similarly 
in its proclivity to neoplasms, it likewise takes after the vagina. As the 



THE GENESIS OF MALIGNANT TUMOURS 159 

portio projects into the vagina, it is, in fact, capped by an upward 
extension of the epidermoidal-celled, dermo-papillary, vaginal lining 
membrane. In the development of papillated structures like the portio, 
the epidermis plays an important part. It causes these structures to 
arise by processes of its proliferous cells, growing into the subjacent 
mesoblastic corium. In this process, " rests " of these ingrowing 
epidermoidal processes are commonly sequestrated, and included in the 
nascent corium ; where, in post-natal life, they may subsequently be 
recognized by histologists as '' pearls," or other non-integrated epider- 
moidal structures. Pre-natal " rests " of this kind, are of common 
occurrence in and beneath the corium of the portio and adjacent struc- 
tures. As we have seen, epidermoidal elements of this kind are the 
germs whence many cervical and some corpus cancers arise ; hence, it 
may be inferred that it is to this source, rather than to the normally 
integrated elements of the mucosa of the portio, that we must look for 
the germs of most epidermoidal cancers of this part. 

In addition to this variety of epithelioma, other forms also originate 
from this part of the uterus. Under certain pseudo-pathological con- 
ditions, which I will now proceed to describe, the cylindrical epithelium 
of the cervix encroaches upon the epidermis-covered territory of the 
portio ; and, from this foreign element, cylinder-celled cancers arise, 
analogous to those that spring from the cervix. So common is this 
invasion of the portio, that the majority of its cancers originate from this 
source. 

It seems probable that most of these aberrant elements, are the 
outcome of pre-natal developmental irregularities. At an early stage of 
embryonic life, the upper part of the vagina, as well as the cervix, is lined 
by cylindrical epithelium. In the subsequent transformation to the 
flattened variety, minute islets of the original cylindrical cells may still 
persist unchanged. Klotz and others have demonstrated conditions of 
this kind in adults ; while Fischel has shown that in young infants, 
cylindrical epithelium is usually found occupying the portio, for a con- 
siderable distance beyond the os externum. 

An analogous condition results from the invasion of the portio by 
offsets of the cervical glands (the so-called " erosions ")>. which so fre- 
quently appear during post-embryonic life in consequence of hyper- 
plastic changes ; as well as from the somewhat similar state that ensues 
from partial prolapse (" ectropion ") of the cervical mucosa whether 
merely the result of tears etc., during parturition, of cystic disease, or 
of other pathological states. Moreover, the minute cysts (" ovula 
Nabothii ") so frequently met with in the lower part of the uterus, which 
are obviously sequestrations from the glands of the cervix, must also be 
borne in mind, for cancers have been shown to originate from them. 

Here it may be mentioned that Nichols * has produced cysts of this \ 
kind experimentally, by transplanting grafts of the uterine mucosa into 
various situations. 

Recent researches indicate that these acquired forms of heterotopia, 
like those previously mentioned, are also really of pre-natal origin, the 
1 Third Report of the Croft Cancer Committee, Boston, U.S., 1905, p. 117. 



160 THE NATURAL HISTORY OF CANCER 

inherent flaw simply being made manifest by the supervention of other 
pathological changes. Even " lacerations " may often be of embryonic 
origin, for Fischel has demonstrated the occurrence of congenital fissures, 
in exactly the situations usually occupied by these so-called lacera- 
tions. 

From the foregoing it will be gathered, that in all cases in which we 
have been able clearly to trace the genesis of cancer in the different parts 
of the uterus corpus, cervix and portio the germs of such tumours 
have proved to be, not the normally integrated, pre-existing, epithelial 
cells of the part ; but rather non-integrated " rests," detached from their 
normal connexions during pre-natal life. This being so, we are I believe 
fully justified in assuming, that the germs of all malignant epithelial 
uterine tumours are similarly conditioned ; indeed, the more carefully we 
consider the significance of the ensemble of ascertained facts and indica- 
tions as bearing on this subject, the more strongly is the truthfulness of 
this conception impressed upon us. 

In short, I think there can be no doubt, that pre-natal developmental 
irregularity presides at the genesis of all uterine tumours. 



Uterine Tumours, and Gross Developmental Irregularity of the 
Uterus etc. 

I now pass to the consideration of the connexion between uterine 
tumours, and certain gross developmental irregularities of the uterus and 
other parts, with which these tumours are fairly often concomitant. In 
the absence of the requisite data, it is for the present impossible to ascer- 
tain the exact proportion of cases in which this concomitancy occurs. 
It would, however, be a mistake to suppose, on account of the com- 
paratively few instances of this kind noted by the older gynaecologists, 
who made special studies of uterine malformations (Kussmaul, Fiirst 
etc.), that this concomitancy is rare ; for, in those days, when the terato- 
logical aspect of the subject was the only one in the specialist's mind, it 
is hardly likely that the presence or absence of tumours would have 
attracted much attention. It accords with this, that of six specimens 
illustrative of uterine malformations, in the broad-minded Cruveilhier's 
great work, 1 two were complicated by myomata and one with double 
ovarian cystoma. But the best proof of all is, that within the last few 
years over a hundred instances of this concomitancy have been recorded. 
Hence, it seems to me as clear as it possibly can be, short of actual demon- 
stration, that these developmental irregularities predispose to tumour 
formation. 

Myoma. Uterine duplicity is the commonest type of malformation 
concomitant with myomata ; and some idea of its frequency may be 
gathered from the fact, that without any attempt at an exhaustive 
search, I have gathered notes of over fifty cases. In this list all the 
different grades of duplicity are represented, from the most complete 
type as represented by uterus didelphys (cases by Clay, Galabin, G. B. 

1 Anat. Path, du corps humain, 1829-1833, t. i., liv. iv., pi. v. 



THE GENESIS OF MALIGNANT TUMOURS 



161 



Johnston, Lewers, Graverry, Munde, Lyle, Pick etc.), to the least as 
represented by uterus introrsum arcuatus (Flatau). But most cases are 
met with in uterus bicornis, which is the commonest variety of this type 
of malformation (Foisy, Falk, Eberlin, Doran, Lockyer, Gow, Boni, 




Martin, Meurer, Gunsett, Wagner, Heinricius, Cruveilhier, Snegurieff, 
Gibson, Clark, Pauchet etc.). 

In an interesting case by Clay, 1 double uterus and vagina was 
associated with uterine myomata, and absence of one kidney. In a 
1 Lancet, 1877, vol. ii., p. 87. 



162 THE NATURAL HISTORY OF CANCER 

v uterus didelphys, Czerwenka J found two myomata of the left corpus, 
concomitant with cancer of the left cervix. 

In G. B. Johnston's case, 2 one compartment of the double uterus 
contained a full-term foetus, which was delivered by Csesarean section, 
while the other compartment was merged in a large myoma, which was 
removed, with the malformed organ, by hysterectomy. In uterus 
bifidus, Pauchet found right-sided myoma, with left-sided pregnancy. 

Pick 3 has reported cases in which the myomatous tumour lay in the 
septum, between the bodies of the two uteri ; and other cases of this kind 
have been met with by Lockyer, 4 Clark, J. Schmidt (adeno-myoma), 
Gunsett etc. In these cases, the germ of the tumours must have been in 
position, as early as the second month of pre-natal .life, when the 
coalescence of the Miillerian ducts begins. 

Several instances of the development of myomata in the unicorn 
uterus have also been reported of late : e.g., in the rudimentary horn by 
Routh, Doran, Mackenzie, Romiti, Mangiagalli etc. ; in the developed 
horn by Bland-Sutton ; and in the cervix, which was replaced by a 
mesonephric adeno-myoma, by Josephson etc. 

In some of the foregoing cases, the vagina also was absent or atresiac 
(Mangiagalli, Eberlin) ; while cases reported by Martin, Jenks and Guyot, 
were concomitant with vaginal absence, the uterus being normal. 

Uterine myomata have also been found in association with con- 
genital atresia of the uterus (Dreykorn), congenital ante-flexion (Thomas), 
in the " infantile " uterus (Keiffer) ; while Jackson has reported myomata 
of an atresiac " infantile " uterus, in which cancer was also present. 

But the most remarkable instance of this type known to me, is the 
case reported by Lynds, 5 in a woman aged forty-five, with a large myoma 
of three years' duration, occupying the site of the absent uterus ; who 
had, nevertheless, lived for nineteen years in wedlock without being 
aware of any physical defect, although she had never menstruated and 
had never been pregnant. It was found, in the course of the operation, 
that the vagina also was absent, as well as all the uterine appendages ; 
and, of the ovaries, the only trace was a small rudiment of one. 

I have previously referred to myomatous tumours connected with 
such malformations as uterus accessorius, bifid and trifid uterus etc. 

In a pseudo-hermaphrodite, aged fifty, in whom the female type 
appeared to predominate, Griiner found myomata of the malformed 
uterus ; and, in another person, aged forty-nine, with a similar defect, 
Howitz met with a tumour the size of a cocoanut, due to myomatous 
disease of the unicorn uterus. In the latter case the left tube was absent, 
the ovaries were represented merely by small nodules, remains of 
Gartner's ducts were found in the vaginal walls, and there was hypo- 
spadias with hypertrophy of the clitoris. Neumann has described 
myomata of the uterus and tube, concurrent with Wolffian " rests " in 
both ovaries ; and Russell has reported the finding of Miillerian relics in 

1 Monats. f. Geb. u. Gyn., Bd. xx., Heft 5. 

2 Trans. Southern Surg. and Gyn. Association, Richmond, Va., U.S., 1900. 

3 Monats. f. Geb. u. Gyn., October, 1897 ; also Arch. f. Gyn., 1896, Bd. lii., S. 389. 

4 British Journal of Obstetrics, etc., 1905, vol. vii., p. 172. 

6 Journal of the Michigan State Medical Society, U.S., March, 1905, p. 122. 



THE GENESIS OF MALIGNANT TUMOURS 163 

the ovary, whence structures like utricular glands had evolved, resembling 
the epithelial inclusions found in some myomata. Wetherill, in removing 
a large myomatous uterine tumour, noticed supernumerary oviducts 
and hydatids. 

This leads me to remark on the frequency with which uterine 
myomata are complicated with ovarian cystomata (often bilateral), 
dermoids, and cysts of the adnexa broad ligaments, round ligaments, etc. 

Of his operated uterine myomata, Pean found associated ovarian 
cystomata in 12-5 per cent. ; and of Winckel's ovarian cystoma, 18 per 
cent, were concurrent with myoma uteri. 

In a remarkable case reported by Buffett, the combined weight of the 
associated tumours amounted to no less than 216 pounds, the left 
ovarian cystoma weighing 180 pounds, and the uterine myoma 36 pounds. 

In the case of a negress, with an enormous cystic myoma weighing 
135 pounds, as described by Stockard, the uterus also contained several 
solid myomata ; and besides there was a small myoma of the left Fallopian 
tube, a cyst of the corresponding broad ligament, and cystic disease of 
the left ovary. 

Leo has found myomata of the uterus coexisting with cystoma of 
the right ovary, and polycystic disease of the left kidney. I have 
previously had occasion to refer to Mear's case, in which the uterus, 
ovaries and kidneys were concurrently affected with congenital poly- 
cystic disease, as if from some developmental irregularity involving 
the whole Wolffian body. Flatau has found a similar type of cystic 
uterine disease concomitant with myoma of that organ ; while Doleris 
and Algret report the concurrence of uterine myomata, with congenital 
polycystic disease of both kidneys. 

Thornton has seen multiple uterine myomata associated with a large 
multilocular cystoma of the right ovary, a cyst of the right broad 
ligament, and multiple cysts of the left ovary ; and, in Hodge's case, 
uterine myomata were associated with cystic disease of the ovary and 
broad ligament. 

Dartigues and Claisse have reported an instance, in which a large 
uterine myoma coexisted with an enormous multilocular cyst of the left 
ovary, and a dermoid of the right. 

Emmet has seen a large cystic myoma of the fundus, with several sold 
myomata adjacent to it, and a polypoid intra-uterine myoma, concomi- 
tant with multilocular cystoma and dermoid of the right ovary. In 
many cases, uterine myomata and ovarian or broad-ligament dermoids, 
have been found concomitant (Porter, Mauclaire, Hulke, Gottschalk etc.). 

Amann mentions the association of adeno-myoma of the uterus with 
ovarian dermoid ; Cartez has found uterine myomatous disease, concomi- 
tant with a piliferous dermoid of the connective tissue, beneath the 
peritoneum of Douglas's pouch ; and Berger met with a para-uterine, 
piliferous pelvic dermoid, which comprised a piece of bone bearing two 
teeth, concomitant with myoma of the corpus uteri. 

Fatty tumours of the para-uterine connective tissue, in association 
with myoma uteri, have been described by Roux and Ullman. 

Myomatous tumours of the uterus, with bipartite bladder, have been 

112 



164 THE NATURAL HISTORY OF CANCER 

reported by Knox ; and by Garrigues, the same disease has been seen 
with the foetal type of bladder. Thorne found uterine myomata 
coexistent with ossifying myoma of the bladder. 

The frequency with which uterine myomata are multiple, might of 
itself lead us to suspect the association of developmental irregularity, 
with the origin of these tumours ; and the occurrence of instances in which 
the whole musculature is converted into a dense mass of small tumours, 
to which I have previously called attention, points to the same conclusion. 

Of like import is the finding of uterine myomata concomitant with 
similar tumours in the ovary, broad ligament, round ligament, tube, 
vagina, and in other situations adjacent to the uterus, of which many 
examples have been recorded. 

Thus, Neill has met with a case in which myomata coexisted in the 
uterus, broad ligaments, and ovaries ; while Virchow long ago reported 
an instance in which the uterus, ovary and vagina were concurrently 
affected. 

Epithelioma (vel Carcinoma). In like manner with the foregoing, I 
know of many instances in which primary malignant epithelial tumours 
of the uterus, have been found in association with gross local develop- 
mental irregularities. 

Thus, examples of the concurrence of cancer of the cervix with the 
various forms of uterine duplicity, have been recorded by Czerwenka, 1 
Rossa, 2 Pollosson, 3 Huber, 4 Biehl, 5 Zweifel, 6 Hasse, 7 Janvrin, Orthmann, 
Alexander, Wertheim, Penrose, Vineburg and others. In cases by 
Czerwenka and Jackson, both cancer and myomata were associated 
concurrently with uterine developmental defects. 

Instances of cancer of the unicorn uterus have been reported by 
Heinricius and Josephson. In a patient who died of cancer of the colon, 
Mackenzie found a myomatous tumour of the one-horned uterus. 

In a case of vaginal atresia, Sandheimer met with cancer of the corpus 
uteri ; and Neugebauer has seen uterine cancer, in a pseudo-hermaphrodite 
with hypertrophy of the clitoris. 

The concurrence of vaginal cancer and uterine myomata, has been 
noted by Warder. In a patient with cancer of the uterus, Amann found 
double ureters on the left side. 

I have elsewhere referred in some detail, to the association of uterine 
cancer with other uterine, ovarian, and pelvic tumours, including 
dermoids. 

These items show, that there is a certain connexion between develop- 
mental irregularities and cancer formation. 

1 Double uterus and vagina, cancer of left portio, two myomata of left corpus 
A Gyn., 1900, No. 7). 

Jterus bicomis, atresia vaginae, absence of left kidney and ureter, cancer of 
cervix (Cent. {. Oyn., 1894, No. 18). 

Bifid uterus, cancer of cervix (Lyon Mid., 1899, t. xc., p. 125). 

Uterus didelphys, cancer of one cervix (Arch. f. path. Anat., 1887, Bd. cviii., S/124). 
Uterus bicornis unicollis with cancer of cervix two cases (Mittheil. d. Vereins 
d. Aerzte, etc., 1894, No. 4, p. 103). 

Uterus duplex, cancer of cervix (Cent. f. Gyn., 1888, p. 47). 

Uterus bicornis, defective development'of right kidney, cancer of cervix (Deutsche 
Klin., 1860, vol. xii., p. 329). 



THE GENESIS OF MALIGNANT TUMOURS 165 

Sarcoma. In a few cases, uterine sarcomata have also been found in 
association with various developmental defects ; thus, Howe x and 
Czerwenka have seen sarcoma concomitant with double uterus, and 
Briesky the same disease with " septum vaginae retro-hymenale." 
Flatau, in each horn of uterus introrsum arcuatus, found a myomatous 
tumour, from one of which sarcomatous disease had originated. Braxton 
Hicks had described a case of congenital absence of the uterus, tubes, and 
ovaries, in which a large cystic myxo-sarcoma occupied the place of the 
absent uterus. 

These examples suffice to show, that this form of malignant uterine 
disease may also be associated with gross developmental irregularity. 

This concludes the evidence at present available, as to the association 
of the origin of uterine tumours with pre-natal developmental irregu- 
larities ; but, no doubt, when attention has once been directed to this 
matter, additions will be made to the weighty items above adduced. 
However this may be, in their ensemble, these facts of themselves suffice 
to prove the correctness of our hypothesis. 



Mammary Tumours and Developmental Irregularity. 

The ordinary anatomical description of the female mammary gland, 
as a flattened disc-shaped mass, is certainly very misleading. The truth 
is that the mamma, like the lachrymal and salivary glands, is normally a 
very imperfectly integrated organ, for its constituent lobules, instead 
of being compacted together in a small space, are generally widely 
diffused ; moreover, in the corpus mammce, its vicinity, and in the axilla, 
detached glandular structures are of common occurrence. It seems 
certain, as I have elsewhere shown, 2 that most of these redundant 
glandular structures are derived by sequestration from the matrix of the 
evolving gland, during pre-natal life. Besides these anomalies, we know 
from studying the embryology of the mamma, that the ducts of some of 
its component lobules, instead of being integrated with the majority of 
their congeners, are nearly always left behind when the nipple is upraised ; 
and open about its base, rather than with them at the apex of the nipple, 
where they are known as the glands of Montgomery, which really are 
glandulce lactiferce aberrantes. 

It has been shown by Schultze, Kallius and Schmidt, that in human 
beings, as in polymastic animals the first mammary rudiment presents 
as a linear thickening of the epidermis, which extends on each side 
from the base of the evolving anterior extremity to the inguinal region : 
this is the " mammary ridge," or common rudiment of the mammary 
glands. In human beings, spindle-shaped thickenings appear at 
intervals, during the second month of pre-natal life, in the course of each 
milchlinie. After a time, the connecting strands usually disappear ; and 
only as many lenticular thickenings persist, as correspond to the number 
of mammae normal in post-natal life. These linear ridges at first occupy 

1 Boston Medical and Surgical Journal, 1876, vol. xcv., p. 224. 

2 " Diseases of the Breast," 1894, chap. iv. 



166 THE NATURAL HISTORY OF CANCER 

a dorsal position ; but subsequently they migrate towards the ventral 
surface. It is easy to understand how, in the course of these modifications 
and migrations, portions of the matrix may be detached and left, in the 
axilla, or in other positions, where they subsequently give rise to 
aberrant glandular structures. Thus there are several ways in which 
mammary glandular " rests " may originate. In the axilla and its 
vicinity, detached glandular structures of this kind, which not unfre- 
quently secrete milk during lactation, are by no means rare, as I have 
shown in my book on " Diseases of the Breast," l where many examples of 
this kind are cited. 

In the corpus mammae and its vicinity, similar mammary glandular 
sequestra have also been noted. " True adenoma " is the name given by 
some pathologists to mammary tumours, structurally exactly like a 
segment of the breast itself ; but not in organic continuity with the 
mamma and its ducts. Tumours of this kind are not particularly rare ; 
and, it is such as these, that occasionally secrete milk (so-called " milk- 
secreting adenoma," some galactoceles etc.). A thorough examination 
of this subject, in connexion with my investigations relating to super- 
numerary mammary sequestrations, has convinced me, that, in these 
cases, we have to do with overgrown mammary '' rests," rather than 
with true neoplasms. Such is the nature of two remarkable cases of 
" milk- secreting adenomata," reported by Birkett ; 2 of a case of "true 
adenoma," described by D'Arcy Power ; 3 and of a milk-secreting cyst, 
found in a cystic sarcoma by Billroth. 4 Examples of tumour-like swell- 
ings of similar origin, in other parts of the breast and its vicinity, have 
been recorded by Oilier, Labbe and Coyne, Eve, Liicke, Forbes, Cameron, 
and myself (from a specimen in University College Museum), as detailed 
in my book on "Diseases of the Breast." 5 It seems certain that the 
germs of these redundant mammary glandular structures, must have 
been detached from the matrix of the evolving gland, in early pre-natal 
life. 

That tumours identical in structure with mammary tumours 
frequently arise from " rests " of this kind, I have clearly proved in my 
above-mentioned work on " Diseases of the Breast." In fact, of the 
mammary tumours specially examined by me ad hoc, I was able to deter- 
mine that 14 per cent, of the nbro-adenomata, and 9-8 per cent, of the 
malignant epithelial tumours, thus originated ; 6 as well as to indicate 
several instances of adeno-sarcomatous and adeno-myxomatous tumours 
similarly derived. This being so, it seems not unreasonable to assume, 
that the germs of most mammary tumours are similarly conditioned. 

It accords with this, that other remarkable instances of heterotopia 
are also met with in the breast, and its tumours. 

Thus Rindfleisch, Hacker, Astley Cooper and others, have found 

1 Chap, iv., 4 and 5. 

2 Guy's Hospital Reports, 1855. 

3 Transactions of the Pathological Society, London, 1885, vol. xxxvi., p. 411. 

4 Arch. f. path. Anat., Bd. xviii., S. 68. 

5 Pp. 63, 73, and 462. 

6 For recent cases of this kind, vide Savariaud (BuU. et Mem. Soc. Anat., Paris, 1906, 
No. 6, p. 476); and Graham (Journal of American Medical Association, August 27, 1898), 
with references to other cases of this kind in the axilla. 



THE GENESIS OF MALIGNANT TUMOURS 167 

cartilaginous, ossiform, calcareous, and even truly osseous structures, 
embedded in the otherwise normal mamma, usually in the form of localized 
deposits ; but Bryk, Berard, and others, have met with diffuse calcifica- 
tion, sometimes in combination with true ossification. 

The most feasible explanation of the presence of these anomalous 
formations in this situation, is that which ascribes their origin to the 
sequestration of sclerogenous elements from the matrix of the evolving 
thoracic skeleton, in early pre-natal life ; and their subsequent inclusion 
in the nascent mammary rudiment. 

It seems certain that the various chondromatous and osteomatous 
tumours, primarily arising in the breast, of which Leser, 1 Hacker, Pied, 
Lange, Cruveilhier, Cambria, Stefanini, Astley Cooper, Nelaton, Warren, 
Wagner, J. Muller, Morgagni and others, have reported examples, origi- 
nated from aberrant elements of this kind. 

These cartilaginous and ossifying tumours, as I have previously 
pointed out, are especially common in the mammae of the female dogs ; 
in which they are often associated with various forms of malignant 
disease, as well as with adenoma. 

In humanity " mixed tumours " of this kind also occur ; thus, instances 
of malignant epithelial tumours concomitant with heterotopic cartila- 
ginous and osseous structures, have been reported by Coen, Gross, Hacker, 
Warren, Heurtaux, Wagner, Busch etc. In such cases, the cancerous 
disease probably originated from glandular structures, displaced from 
their proper connexions by entanglement with skeletal sequestra : in 
Heurtaux's case, glandular cancer was concomitant with ossifying and 
chondrifying sarcoma, as was proved by the. nature of the secondary , 
growths, which reproduced the peculiarities of the primary tumour. Y ' 

In mammary sarcomata similar foreign elements have been found 
by Arnold, Stilling, C. A. Morton, Routier, Bowlby, Pilliet, Coats, Battle, 
Lecene, Hueter, Durham etc. ; small calcareous concretions in these 
tumours have been seen by Olivier, Neugebauer, Ackermann etc. ; 
while, in Dubar and Clarke's cases, extensive areas of the neoplasm were 
calcified. 

In myxomatous tumours, similar structures have been noted by 
BiUroth, Leloir etc. 

Gross and Durham, in fibro-adenomata, found similar conditions 
(osseous heterotopia) ; and in both these cases sarcoma subsequently 
supervened. 

A remarkable instance of a different kind of heterotopia, has been 
published by Billroth : in a small round-celled sarcomatous growth 
removed from the breast of a girl aged sixteen, he found numerous 
transversly striated, spindle-shaped muscle cells. In this case, it seems 
probable that the foreign elements were derived by sequestration from 
adjacent transversely striped muscle matrix, detached during the 
changes incidental to mammary development, in early pre-natal life. 

In like manner, dermoid cysts of the breast no doubt arise, by seques- 
tration from the epiblastic rudiment of the evolving gland in pre-natal 

1 For details and bibliographical references to cases cited in this section, the reader 
is referred to my book on " Diseases of the Breast." 



168 THE NATURAL HISTORY OF CANCER 

life, of which examples have been recorded by Rocher, D'Or, Hermann, 
Ribbert, Reverdin and Mayor, Van der Byl, Albers, Velpeau, Gerdy, 
Guyot and others. All of these were simple epidermoidal cysts, with 
the exception of Albers', which was also piliferous. 

In several instances heterotopic epidermoidal formations, have been 
found comprised in fibro-cystic and fibro - adenomatous tumours 
(J. Griffiths, Borst, Haeckel etc.) of this part. 

A similar concomitancy of dermoid cyst, with adeno- cystic sarcoma of 
the mamma, has been seen by J. Miiller ; and in cystic sarcomatous 
tumours of this part, Borchmeyer, B. Schmidt, Model, Grohe, Kiirsteiner, 
Ribbert, Lecene, Wilms and others, have met with epidermoidal " rests," 
hornifying pearls etc. 

It is to epidermoidal " rests " such as the foregoing, that we must look 
for the germs of the rare primary melanotic tumours of the mamma, of 
which examples have been studied by Cornil, Billroth, and Gurlt. 

Thus for mammary, as for uterine tumours, I have shown that a con- 
siderable proportion arise from aberrant structural elements, detached 
from their normal connexions during pre-natal life, owing to develop- 
mental irregularity ; and these tumours all bear the impress of their origin, 
visibly stamped in their structure. This being so, it may be inferred that 
even tumours in which this impress cannot be detected, nevertheless, 
have their origin similarly conditioned. 

Moreover, there are just as good reasons for believing, that what is 
true for the origin of uterine and mammary tumours, is equally valid 
for the origin of all tumours. 



CHAPTER VIII 
THE EXPERIMENTAL STUDY OF CANCER GENESIS 

IT must be confessed that the results of the many attempts which have 
been made to produce histioid tumours experimentally whether by 
implanting normal tissue elements, or those derived from tumours, or 
by injecting the cultures of various so-called " cancer microbes " have, 
on the whole, been disappointing. 

So far as malignant tumours are concerned, the results have hitherto 
been entirely negative, although some pathologists claim to have met 
with positive results, of which more anon. 



Experiments with Normal Tissue Elements. 

Epidermoidal tissues are remarkable above all others for their great 
regenerative power, and for their tenacious vitality ; while the facility 
with which even large pieces of skin may be transplanted, is well known 
to surgeons, who have practised the plastic methods of Thiersch, 
Reverdin, Oilier etc. 

Even epidermoidal scrapings, the shavings of warts, dried bits of 
cuticle separated by burns, 1 the cuticle raised by blistering etc., have been 
successfully employed for healing ulcerated surfaces, by grafting them 
thereon. Recent experiments as to the limit of the vitality of the skin 
after its removal from the body etc., have greatly altered old ideas as to 
the possibilities in this direction. Thus, pieces of skin from amputated 
limbs have been found to retain their vitality, for thirty-six hours after 
their removal from the body (Brewer) ; and, when suitable temperature 
and other conditions have been maintained, for much longer periods 
e.g., for ninety-six hours (Marten), for several weeks (Wentscher), or even 
for several months (Ljunggren). 

Of all the tissues of the body, the epithelial ones have, on the whole, 
departed less from the primordial cellular type than any others, and their 
constituent elements (" labile ") are constantly proliferating during the 
whole life of the individual ; hence their cells still retain their primitive 
powers of growth and reproduction in higher degree than any others. 
Thus may we account for their great regenerative power, their remarkable 
vital tenacity ; and to this source may also be ascribed their undue 
proclivity to malignant and non-malignant tumour formation. 

1 Lusk found that such separated cuticle retained its vitality, and grew when grafted, 
even five weeks after its separation (New York Medical Journal, December 21, 1895, 
p. 799). 

169 



170 THE NATURAL HISTORY OF CANCER 

It has been observed of many tissue transplantations, that they 
have succeeded much better when pre-natal grafts were employed, than 
with grafts derived from the post-natal period.{- '" ^~^^^^J^^^ 

With regard to epidermoidal transplant ation7 it is doubtful whether 
any such distinction is valid ; at any rate, some of the most successful 
results have been attained with post-natal elements. 

When pieces or small fragments of epithelial tissues, derived from early 
pre-natal life, are transplanted or injected into adult animals, most of 
these grafts grow and even undergo a certain amount of differentiation, 
similar to what they would normally have undergone, had they retained 
their normal connexions ; thus, in grafts of this kind, transplanted 
epithelial cells have even been known to assume the glandular form etc. 
After a time, however, their constituent cells generally cease to grow, 
and are eventually absorbed. . In some instances, most of the grafts 
degenerated from the start, such growth as subsequently supervened 
taking place from the surviving elements (Barfurth, Fere, Loeb, Lubarsch, 
Levin, Masse etc.). 

In a few instances, it appears that epidermoidal cysts have resulted 
from experiments of this kind ; but, as to the permanence of such 
artificially produced new formations, there is need of further evidence^ 
Certainly, no other kind of non-malignant epithelial tumour has ever been 
produced in this way ; and, above all, nothing like cancer has ever resulted. 

By implanting into the peritoneal cavity of young white rats, bits of 
skin and parts of limbs of newly-born rats, Masse * succeeded in artificially 
producing epidermoidal-lined cysts, containing hairs, epidermoidal debris 
and cholesterine : such were the conditions found, when the animals were 
killed, two and a half months after the initial operations. In like manner 
he succeeded by subcutaneous grafts, in artificially producing subcu- 
taneous " pearly " tumours. 

Levin, 2 by transplanting small pieces of foetal skin into the peritoneal 
cavity of rabbits, in two cases found that one or more epidermoidal 
" pearly " tumours resulted. 

Nichols, 3 having transplanted epidermis from a foetal rabbit, into the 
subcutaneous tissue of the ear of its mother, saw a " pearly " tumour 
form from the graft, which grew more quickly than when post-natal 
epidermis was used for the experiment. 

Similar experiments, with post-natal epidermoidal tissues, have given 
almost identical results (Kaufmann, Ribbert, Schweniger etc.). 

Kaufmann 4 made numerous experiments to ascertain the fate of 
embedded skin, employing chiefly the combs and wattles of fowls, which 
are very vascular tissues. Islands of surface skin were circumscribed by 
continuous incision ; flaps were raised on each side and united by sutures 
over each cutaneous island, which still maintained its normal relations 
with its connective-tissue substratum. 

Kaufmann found that the rate of increase of the embedded epidermis 

1 Bull. gen. de therap. Med. et Chir., 1885, t. cviii., p. 337. 

2 Journal of Medical Research, 1901, vol. vi., p. 145. 

3 Third Report of the Croft Cancer Committee of Harvard Medical School, 1905, 
p. 116. 

4 Arch. f. path. Anat., Bd. xcvii., S. 236. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 171 

was greatly in excess of the normal, the grafts curling up at their margins 
and forming cyst-like structures, resembling the simpler kinds of dermoid V 
cyst. This increase, in some cases, continued as long as 210 days, when a 
stationary condition was attained. 

In connexion with the increased rate of growth here noticed, it is of 
interest to recall John Hunter's experiment, of transplanting the cock's 
spur to its comb ; where it grew to a size much in excess of the normal, 
apparently owing to the increased vascularity of its new substratum. 

Ribbert l cut out skin flaps, and while each was still connected with 
its natural basis by a narrow pedicle, it was introduced into the abdominal 
cavity, where each quickly adhered by its connective-tissue surface to 
the peritoneum, enclosing the epidermis in a cyst-like cavity. When 
these inclusions were examined after a sufficient lapse of time, they were 
found to have been converted into epidermoidal- lined cysts, with hairs 
growing from their walls, which contained epidermoidal debris etc. 

Marnoch, 2 however, repeating experiments of this kind on guinea- 
pigs and rabbits, found in every case that the embedded tissue was 
quickly absorbed. 

The possibility of the experimental production of epidermoidal cysts, 
and " pearly " tumours, is confirmed by the fact that tumours of this 
kind have often formed after certain traumata, in consequence of portions X 
of epidermis being displaced from their normal connexions, and implanted 
amidst other tissues. 

Most instances of this kind have been met with in the hand (especially 
the palmar surface of the digits) and iris ; but also in other parts (vagina, 
cornea, thorax, thigh etc.). 

These implantation cysts usually contain turbid or milky fluid, with 
pearly white, laminar epidermoidal tissue, within a fibrous pseudo- 
capsule : the polymorphic, epidermoidal cells are arranged in successive 
layers, the deeper ones of cubical or columnar form, merging gradually 
into hornified cells, as described by Polaillon (1884). In exceptional 
cases fragments of cutis vera are implanted, which may sometimes 
maintain a connexion with the surface skin : in the walls of such cysts, 
papillae, glands, and even hairs, have been seen. Instances have also been 
reported in which the foreign body causing the implantation, has been 
found in the tumour ; thus, Mr. C. A. Morton, 3 met with a thorn in the 
midst of the cornified, laminated matter, from a tumour of this kind in 
the thigh, which was known to have existed for nearly thirty years. 
Condon 4 has reported an example of an epidermoidal cyst of the anterior 
thoracic wall, secondary to fracture of the adjacent ribs. In bovine 
animals, piliferous subcutaneous cysts have been seen, which appeared 
to have resulted from skin implantations, caused by the drovers prodding 
the animals with the sharp goad. 

The traumatic origin of implantation cysts of the iris was first indicated 
by Hulke (1869), who ascertained that in fifteen out of nineteen recorded 
cases, some form of penetrating wound had preceded the appearance of 

1 Deuteche med. Woch., 1895, Nos. 1, 2, 3, and 4. 

2 Lancet, 1901, vol. ii., p. 6. 

3 Bristol Medico-Chir. Journal, 1894, vol. xii., p. 252. 

4 Journal of Pathology, etc., 1901, vol. vii., p. 368. 



172 THE NATURAL HISTORY OF CANCER 

the tumours, whose epidermoidal structure he determined. The germs 
whence these cysts arise are displaced bits of corneal, conjunctival, or 
even eyelid cuticle. In several cases they have been found associated 
with a displaced eyelash, carried into the eye by the wounding agent. 
The correctness of this aetiology has been experimentally proved by 
Masse (1881), who caused tumours of this kind by grafting bits of 
conjunctiva into the iris of rabbits etc. 

1 1 have previously referred to the artificial production of uterine cysts, 
by the implantation of grafts of uterine mucosa. 

A sensation was caused among pathologists some years ago, when 
Lack l claimed to have succeeded in experimentally producing cancer, by 
intra-abdominal auto-implantation in a rabbit. 

Having opened the peritoneal sac and bisected each ovary, the raw 
surfaces of the latter were freely scraped with a sharp knife, the detached 
juicy and parenchymatous ovarian products being diffused throughout 
the peritoneal cavity. The abdominal wound was then closed, and the 
animal recovered. It remained well for a year, but then got thin and 
weak ; and was killed in this condition fourteen months after the 
initiation of the experiment. At the post-mortem examination, the 
peritoneum was found studded with tumour-like formations, as well as 
the liver, diaphragm, mediastinum and uterus. Histologically examined, 
sections of these growths presented the appearance of alveolar spaces, 
lined by one or more layers of columnar epithelial cells. Other patho- 
logists who have repeated this experiment, and various modifications of 
it, have failed to reproduce similar morbid appearances : their grafts 
etc., after a time, completely disappeared (Levin, Basso, Shattock, 
Nichols, Enderlin, Ribbert etc.). 

I have previously referred to possible explanations as to Lack's 
success ; which, in the absence of corroboration, cannot be accepted as 
an example of the experimental production of cancer. 

It accords with this, that experiments made on other parts of the 
body with the same object in view, have yielded only negative results. 
Thus the attempts of Gilbert and Roger to produce cancer of the mamma, 
in old bitches, by subjecting the part to various forms of mechanical irrita- 
tion, completely failed ; and Cazin, by rubbing soot into irritated parts, 
was equally unsuccessful, although the soot particles were taken up by the 
local cells, as is known to be the case in that form of cancer of the scrotum 
called " chimney-sweep's cancer." 

It was just the same with the experiments of D'Arcy Power, 2 Pier- 
allini and Galeotti. Lately B. Fischer 3 has made fresh experiments : the 
tissues of the rabbit's ear having been injected with a mixture of olive oil 
and the fat-staining dye " Scharlach B," the cutaneous epithelium of the 
part was in this way separated from the subjacent tissues. Soon after- 
wards these epidermoidal cells showed mitoses ; they thickened, ingrowing 
processes appeared, which penetrated the subjacent parts and even 
perforated the cartilage of the auricle, while epithelial pearls formed etc. 
In short, in all of these experiments, the histological appearances of the 

1 Journal of Pathology, etc., 1900, vol. vi., p. 154. 

2 Ibid., 1896, vol. iii., p. 124 ; also 1897, vol. iv., p. 69. 

3 Miinch. med. Woch., 1906, Bd. liii., S. 2042. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 173 

damaged parts were very similar to those seen in malignant epithelial 
tumours. 

Under these circumstances, it is impossible to admit the validity of 
the claims of Hemmeter, 1 Maniscalio, 2 Fiitterer 3 etc., to have caused 
" adeno-carcinoma " of the stomach in various animals by irritating 
artificially-produced ulcers ; for these claims rest solely on the local 
histological appearances, which in the absence of other signs of malignancy, 
are by no means conclusive. 

Some pathologists, experimenting with tissue implantations, have 
reported that grafts into the ovaries grew better than those in other 
localities. Here Loeb's 4 interesting observations, as to the growth of 
epidermoidal cells in blood-serum and in agar must be recalled. In this 
strange environment, the epithelial cells grew and multiplied with great 
freedom quite independently of any connective-tissue substratum 
reproducing most of the histological appearances of epithelioma, as above 
detailed. 

Epithelium in process of regeneration, wherever found, manifests 
similar changes ; and Loeb 5 has specially called attention to certain 
resemblances between the histological appearances of epithelial healing 
and epithelial cancer. 

Lately the interesting discovery has been made that, by treating 
proliferating cells with various poisons and chemical reagents (quinine, 
chloral, cocaine, antipyrin etc.), analogous irregularities in their mitoses 
and mode of growth can be artificially produced, even when quite dilute 
solutions are used. 

It has also been shown by B. Moore that, even the reducing division, 
supposed to be characteristic of reproductive cells, which had hitherto 
only been met with outside this sphere in malignant tumours, can 
also be produced artificially, as well as other karyokinetic irregularities, 
by treating proliferating cells with alkaline solutions of a certain strength. 

These results suggest the possibility, that the similar irregularities in 
the proliferation of the cells of malignant tumours, may be due to the 
presence of some unknown bio-chemical agency. 

Here attention may be called to the fact, long well known to human 
pathologists, that in most chronic hyperplastic processes of epithelial- 
covered parts, quite analogous morphological changes commonly occur. 
Conditions of this kind have been specially studied by Wyss, 6 Fried- 
lander, 7 Councilman 8 and others 

Waldeyer, from the histological standpoint, having proposed for 
cancer the very short-sighted definition of " atypical epithelial prolifera- 
tion," was soon made conscious of the serious inadequacy of such a con- 
ception, by the above-mentioned histological researches, which showed 
that " atypical " epithelial ingrowths were common enough, in many 
chronic hyperplastic processes affecting epithelial-covered surfaces. 

American Journal of Medical Science, April, 1903. 3 Rif. Med., April 1, 1905. 

" liber die Aetiologie des Carcinoms," etc., 1903. 

Journal of Medical Besearch, 1902, vol. viii., p. 109. 

Arch. f. Entwickelungs-rnech., etc., 1898, vi., S. 297. 

Arch. f. path. Anat., Bd. Ixix., S. 24. 

" Ueber Epithelwucherung und Krebs." Strassburg, 1877. 

Johns Hopkins Hospital Bulletin, No. 2, 1890. 



174 THE NATURAL HISTORY OF CANCER 

One of the best examples of this is furnished by the so-called 
" erosions " of the portio vaginalis uteri, wherein newly formed structures 
abound, very like cancer structures. These consist of ingrowths of the 
local epithelium, into the subjacent granulation tissue, which is thus 
interpenetrated by branching, anastomosing, ingrowing epithelial 
processes and networks. These are usually hollow, but not infrequently 
also quite solid cellular processes and " nests," may be formed. Thus 
a perfect histological counterpart of the structures commonly met with 
in epithelial cancer of this part may be reproduced ; and yet the con- 
dition is quite innocent, for it lacks the quality of malignancy. This 
quasi-cancerous process is only arrested when the dense connective- 
tissue substratum is reached. It is thus evident, that the epithelial 
proliferation of cancer is not without counterparts, in various other 
morbid processes. 

The knowledge of the foregoing facts enables us to understand how 
quasi-malignant tumours, comprising proliferous epithelial elements, 
may be caused by many various extrinsic agents, e.g., traumatic, 
microbic, chemical etc. Thus, cases of " blastomycetic dermatitis " 
have been described, in which the gross and microscopical features of 
the lesions, were very similar to those of cutaneous cancer (Gilchrist, 
Stokes, Owens, Hyde, Hektoen etc.) ; while infectious quasi-sarcomatous 
tumours, similarly derived, have been met with in men and animals 
(Busse, Curtis, Sanfelice 1 etc.) ; and yet the disease is not malignant. 
In this category the " infective epitheh'oses " of Borrel may also be com- 
prised ; and I have no doubt that " Jensen's tumour " of mice, and Loeb's 
" adeno-sarcoma " of the neck of white rats, are of the same nature. 

From a consideration of the ensemble of the foregoing items, it may be 
inferred that the unknown agent which causes malignant proliferation, 
is not specific ; but rather that any kind of stimulus capable of exciting 
the local cells to undue proliferative activity may suffice. And, since the 
ontological history shows that for the requirements of physiological life, 
intrinsic stimuli are by far the more effective ; so it is likewise probable 
that under pathological conditions tending to tumour formation, the 
same kind of stimuli prevail such as serve as nuclear pabulum probably 
being in the first rank. 

With regard to transplantation experiments with normal connective- 
tissue structures, whether of pre- or post-natal origin, the general outcome 
of many tentatives has been that, although at first the grafts often grew, 
yet, after a time, they were eventually absorbed. 

In these experiments the maximum of success has been with foetal 
cartilage (Zalm, Leopold, Birch-Hirschfeld and Garten). 

Zahn 2 injected into the external jugular vein of rabbits, foetal cartilage 
from the same animals broken up in liquor amnii ; and found, when he 
killed and examined the dead animals a comparatively short time after 
the experiment, numerous cartilaginous nodules in their lungs chiefly 
near the surface. Similar experiments with post-natal cartilage were 
entirely negative. 

1 For details of these interesting cases, vide Chapter X. 

2 " Sur le sort des tissues implant ej dans 1'organisme " (G. E. Cong. rued, internal, de 
Geneve, 1878, p. 658). 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 175 

Leopold, 1 continuing Zahn's line of research, made numerous experi- 
ments as to the effect of implanting foetal rabbit's cartilage into the 
anterior chamber of the eye, the abdominal cavity and the external 
jugular vein, of rabbits. Of these the most successful were the eye 
implantations, some of the grafts increasing even to the extent of two or 
three hundred times their original size, at the same time undergoing 
ossification, and maintaining their vitality for considerable periods. 

Helmholz 2 caused the formation of numerous small cartilaginous 
nodules in the rabbit's ear, by scarifying the cartilage of the same. 

By injecting a mixture of finely chopped-up fowls' embryos in normal 
saline solution into dogs, Ribbert 3 claims to have produced, in a few 
weeks' time, malignant tumours in five out of fourteen dogs experimented 
on. To these claims it may be objected that the lapse of time was not 
sufficient, so many previous experiments having shown that the nodules 
which formed at first were subsequently completely absorbed. 

Birch-Hirschfeld and Garten 4 injected into the liver of rabbits, hens, 
goats, frogs and salamanders, an emulsion of finely divided, mixed foetal 
tissues, variously derived. In a few instances, cartilaginous formations were 
found in the liver and lungs shortly afterwards ; but, they were all event- 
ually absorbed although, in the case of a salamander, a chondromatous 
formation in the liver still persisted forty-one days after the injection. 

In like manner, Nichols 5 found that foetal cartilage from a female 
rabbit, transplanted into the maternal subcutaneous tissue, gave rise to ' 
a considerable nodular growth, in which there was ossification. 

Cohnheim and Maas 6 introduced into the jugular vein of animals, 
portions of the periosteum of the tibia of post-natal rabbits, dogs etc. 
These lodged in the lungs, where they grew for a time, producing cartilage 
and bone ; but, by the end of the fifth week after the experiment, all 
traces of them had completely disappeared. Similar experiments with 
various foetal tissues by Alessandri, Lwoff and Levin and by Ribbert, 
Lubarsch and Levin with post-natal tissues yielded only negative results, 
the grafts being invariably disintegrated and absorbed. 

It was, however, long ago shown by Oilier 7 that detached flaps of 
periosteum implanted into the soft parts, gave rise to bone formation 
in their new situations ; and, even the juice obtained by scraping the deep 
aspect of the periosteum led to bone formation, when it was implanted 
subcutaneously. 

According to Knauer, 8 McCone, 9 Enderlin, Ribbert, and others, when 
entire organs such as the ovary and thyroid are transplanted into the 
same animal, or from one animal to another, they continue to survive and 
to perform their special functions in their new surroundings. Nichols, 10 
and Basso, 11 however, found that when the whole ovary or half of it, was 

Arch. f. path. Anat., 1881, Bd. Ixxxv., S. 283. 

Johns Hopkins Hospital Bulletin, September, 1907, p. 269. 

" Progressive Medicine," 1905, vol. ii., p. 158. 

Znegler's Beitr. z. path. Anat., 1899, Bd. xxvi., S. 132. 

Third Report of the Harvard Croft Cancer Committee, 1905, p. 121. 

Arch. }. path. Anat., Bd. Ixx., S. 161. 

Journal de la Physiologic de Vhomme et des animaux, 1859, t. ii., pp. 1, 169, and 468. 

8 Wien klin. Woch., December 7, 1899. 

9 American Journal of Obstetrics, etc., 1899, vol. xl., p. 214. 

18 Op. cit. u Monat-s. f. Geb. u. Oyn., Bd. xxii., Heft 5. 



176 THE NATURAL HISTORY OF CANCER 

transplanted into the subcutaneous tissue of the same animal, these 
grafts after a sufficient interval of time (up to 101 days) were 
absorbed. Schultz l showed that ovaries transplanted into the peri- 
toneal cavity of male guinea-pigs, dwindled in size and manifested no 
signs of proliferative activity, at the end of eleven days after implanta- 
tion ; but Hunter long ago succeeded in grafting the testicle of a cock 
into the belly of a hen, although experiments of this kind generally failed, 
and the grafted organ " seldom came to perfection." 

Shattock and Seligmann, experimenting with incompletely castrated 
cockerels, found that where minute fragments of ruptured testis under- 
going maturation and gametogenous processes had become grafted on 
the liver, intestine etc., no malignant disease ensued, notwithstand- 
ing the free production of " gametogenous " tissue in the grafts. 
Nichol's implantations of testicular substance into the peritoneal cavity, 
also gave similar negative results. 

By transplanting cross sections of rabbit's and guinea-pig's uterus, 
into the subcutaneous tissue of the abdomen of the same animal, Nichols 2 
produced cystic formations, which were in some instances multiple. The 
lining of these cysts resembled that of the uterine mucosa. The trans- 
planted tissues increased and maintained their capacity for growth in 
most cases, as evidenced by the cellular mitoses, even for a considerable 
time after the experiments ; but, in no case did there result a new for- 
mation having the least resemblance to myoma, or to any kind of 
malignant tumour. 

The possibility of transplanting teeth has been well known, ever since 
the time of Hunter, who not only transplanted teeth, from one part of 
the mouth of the same individual to another part of the mouth ; but also, 
from one human being to another ; from one animal to another, and from 
human beings to animals. In the Royal College of Surgeons' Museum, 
there is a specimen showing the successful transplantation by Hunter, 
of a human tooth into a cock's comb. 3 The tooth grew in its new situa- 
tion, and when the cock died, Hunter injected the tooth through the 
bloodvessels of the cock. The vitality of each part of the body, seems to 
have a certain autonomy. Another curious feature of transplanted teeth 
is, that they may transmit the poison of syphilis. Legros and Magitot have 
shown, that the dental bulbs may also be grafted on to the neighbouring 
parts three out of sixteen experiments being successful. May not dis- 
placed bulbs of this kind be the germs of the peculiar warty growths, 
described by Cock, Salter and others, as sometimes being met with on the 
gums, and on the adjacent parts of the hard palate ? 

Even the extremity of the nose, ear, and the ends of fingers and toes 
including a portion of the bone have been successfully reunited after 
recent severance, sometimes after the lapse of several hours. 

In animals, as the experiments of Bert show, the transplantation of 
parts between animals of the same species, can be readily effected ; thus, 
the denuded tails and feet of rats, were successfully transplanted beneath 
the skin of other rats, as also detached periosteum and teeth. 

1 Cent. f. allg. Path., etc., 1900, Bd. xi., S. 200. 

2 Op. cit., p. 117. 3 No. 47, Pathological Series. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 177 

In none of the foregoing experiments, except in the case of epider- 
moidal cyst formation, was it possible to produce experimentally anything 
that could be properly described as a tumour ; although Leopold's results 
seem to indicate, that transplanted foetal cartilage has some tendency to 
evolve in this direction. 



Experiments with Papillomatous Tumours etc. 

There is probably some basis for the popular belief, as to the occasional 
contagiousness of the ordinary cutaneous wart : thus Dr. Payne l relates 
that, after having used his thumbnail to effect the separation of warts of 
this kind, three similar warts developed under the nail of this thumb. 

Variot 2 has succeeded in experimentally transplanting warts of this 
kind, from an infant to a man : the same author has also met with an 
instance of concomitant warts on the hands and eyelids of a child, in 
which it seemed probable that the disease had been transferred, from the 
former to the latter locality, by auto-inoculation. 

Billroth 3 has noted an instance of the auto-inoculability of these 
warts, thus he says : " I saw a case where an ordinary wart formed on 
the side of a toe ; and, on the part of the neighbouring toe lying in contact 
with it, another wart formed." 

The experiments of 0. Lanz 4 are to the like effect : for, having finely 
chopped up some warts from the hand, he injected the product into the 
subcutaneous tissue of the same person ; and so succeeded in artificially 
producing a fresh crop. Lanz even succeeded in implanting thus a group 
of warts, in the form of the capital letter J, on the back of a gardener's 
hand. Similarly, by rubbing a healthy digit against some of these 
warts, the disease was implanted on the former. 

As all attempts to isolate any microbe from these warts failed, Lanz 
concluded that the epidermoidal cells of the growth were themselves the 
infective agent. In a recurrent wart of the septum nasi, O'Kinealy 5 
found sporozoan parasites ; and Beattie has demonstrated a similar 
condition in cases of aural and nasal polypi. 

It may, however, be inferred, from the fact that Leale 6 and others 
have successfully used cut-up warts, as grafts for promoting the healing 
of ulcerated cutaneous surfaces, without causing any wart formation, 
that the contagiousness of warts to whatever agent it may be due is 
easily destroyed. 

It accords with this, that the contagious properties of these warts are 
seldom very noticeable ; and, as is well known, after a variable time, and 
under circumstances as yet not clearly defined, they commonly disappear 
" spontaneously." Here attention may be called to the not very rare 
occurrence of the outbreak of warts on the. hand, after the making of 
post-mortem examinations and other similar work. 

1 British Jour mil of Dermatology, 1891, vol. iii., p. 186. 

2 J. de Clin. ct de therap. inf., Paris, 1894, vol. ii., p. 529 ; also vol. i., 1890, p. 97. 

3 " Surgical Pathology," 1879, p. 668 (Hackley's translation). 

4 Lkutsche med. Woch., May 18, 1899. 

5 Proceedings of the Laryngological Society of London, 1903, vol. x. 

6 New York Medical Record, September 7, 1878. 

12 



178 THE NATURAL HISTORY OF CANCER 

Another group of papillomatous tumours, which arise from the ovary 
and its vicinity, manifests a higher degree of contagiousness than its 
cutaneous analogue. When fragments of these growths are shed into 
the peritoneal sac, they readily become engrafted thereon, so that very 
formidable-looking, diffuse masses of these warts may be thus produced. 
After removal of the original disease, and detachment of the more 
prominent secondary masses, together with irrigation and drainage, these 
growths generally completely disappear. Very extensive formations of 
this kind, may even sometimes disappear spontaneously, of which 
Cullingworth i and others have described striking examples. 

The facility with which accidentally detached grafts from these tumours 
take root in the track of operation wounds, is well known to surgeons. 

In a case of this kind, with considerable abdominal distension from 
intraperitoneal fluid etc., for which Cullen 2 was obliged to resort to 
paracentesis, papillary growths soon afterwards developed along the 
whole length of the trocar wound. Similar transplantation warts have 
often been known to form, in the scar of the operation wound in the 
abdominal wall ; and, in fact, anywhere in the track of the operation 
wound. Most recurrences after ablation are no doubt of this nature. 

From these clinical experiences, it is safe to predict that if warts of 
this kind were finely chopped up, and the product injected subcutaneously, 
the disease could easily be artificially transplanted in the same individual. 

There is yet another common form of papilloma, which fairly often 
manifests contagious properties, and is transmissible to the same and to 
other persons ; and this is the venereal condyloma. This malady is still 
commonly regarded as a gonorrhoeal, chancrous, or syphilitic manifesta- 
tion ; but this is I believe a mistake. 

Condylomata are not uncommonly transmitted with gonorrhoea and 
syphilis ; but the maladj r is sui generis, and occurs independently, of which 
there are unmistakable instances. It is curious to find that this was 
also the opinion of Astley Cooper ; thus, in his vivacious and interesting 
" Lectures on Surgery," 3 he says : " These warts were formerly considered 
as syphilitic, but you are to learn that they are nothing but a local 
disease, requiring nothing but local means for their cure. Yet, when I 
say local, I must observe that they frequently secrete a matter, which is 
able to produce a similar disease in others. I have known two instances 
of this. Mr. Chandler removed some warts, which were of a very large 
size, from a patient in the hospital ; and, as he was returning the knife, 
his dresser put his hand forwards, and it entered just under the thumb- 
nail. In a little time he had an irritation about the nail, and a wart grew 
out of the part where the puncture had been made. It was frequently 
destroyed ; but each time it grew again. I advised him to put on a 
blister, for the purpose of bringing away the nail, and then that the wart 
might be removed. He applied a blister, and readily removed the nail ; 
but it also brought away the wart, which never grew again." 

" The other case of warts generating themselves, was told me by a 
gentleman in Sussex. He was called to attend a lady in labour ; he 

1 Transactions of the Obstetrical Society, London, vol. xxxiv., p. lot. 

2 " Cancer of the Uterus," 1901, p. 662. 3 P. 556. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 179 

felt something in the vagina, which appeared unintelligible, and on 
examination found it to be a crop of warts. He delivered her, but did 
not say anything about the warts to the lady. In conversation with the 
husband, he told him that his lady had a number of warts. The 
gentleman stated, that at the time he was married he had warts on the 
penis ; and he had no doubt that he had communicated them to his wife. 
It is a common opinion that they are propagated by the blood, but do 
not entertain this idea it is by the secretion of matter." 

The nature of the contagium in these cases is still a moot question ; 
but, as previously mentioned, there are reasons for believing whatever 
it is that it centres in the epidermoidal cells themselves. 

It should also be noted that these warts like their ovarian congeners 
often recur after removal by surgical means. Their structure comprises, 
besides the papillomatous outgrowths, epidermoidal ingrowths and 
" nests." Yet it not unfrequently happens, after a time, that they 
undergo spontaneous resolution. 

In this connexion, it is interesting to recall the fact, that similar 
contagious growths affect the genitalia of dogs and other animals ; and 
are readily transferred from one animal to another during sexual inter- 
course, and by experimental implantation. 

Like their human congeners, these growths after a time commonly 
disappear spontaneously ; and such individuals are then immune to 
reinfection (Sticker). It is generally believed that they cannot be trans- 
planted into any other animals except dogs ; but, according to Sticker, 
a case is known in which a fox was successfully affected in this way. 

The history of the building up of our knowledge with regard to this 
canine malady is very instructive, especially in that the morbid appear- 
ances on histological examination have been so diversely interpreted ; 
thus, the malady has been described by those who have specially studied 
it as epithelioma, carcinoma, sarcoma, lympho-sarcoma, lymphoma, 
endothelioma, papilloma, granuloma, molluscoid etc. 

According to Sanfelice l the malady is a blastomycosis ; while 
J. J. Clarke 2 claims it as a sporozoan infection. 

This shows how little the histological analysis per se, can be depended 
on for diagnosis, in doubtful cases ; and it should make us very cautious 
about accepting as true cancer, the somewhat similar lesions met with in 
mice and rats. 

It was Wehr 3 who first specially called attention to these 
tumours, by announcing that he had succeeded in experimentally 
producing " cancer," by implantation of the disease from the vagina and 
penis into the subcutaneous tissue of the abdomen of other dogs. Of 
twenty-six experiments, twenty-four succeeded ; but, in most cases, 
these grafts subsequently underwent spontaneous resolution. In one 
case, however, the disease progressed, with the formation of secondary 
growths in the adjacent lymph-glands and in the spleen. 

Duplay and Cazin, 4 who studied the malady in 1894, successfully 

1 Eif. Med., 1904. 2 * "Protozoa and Disease," part ii., 1908. 

3 Arch. f. klin. Chir., 1889, Bd. xxxix., S. 226. 

4 Transactions of the Eleventh International Medical Congress, Rome, 1894, 
vol. ii., p. 103. 

122 



180 THE NATURAL HISTORY OF CANCER 

transplanted bits of a growth from a dog's penis, into the subcutaneous 
tissue of other dogs. They describe the disease as infective granuloma. 
They also met with dissemination in one case (testis). 

Geissler 1 subsequently made successful implantations ; and, after one 
experiment, secondary growths in internal organs were found. Like 
Wehr, he regarded the malady as a malignant epithelial tumour. 

Smith and Washbourn 2 made a very thorough study of the condition 
a few years later. They found that in the vagina the tumours often 
attained a large size, infiltrated the walls deeply, and were frequently 
ulcerated. In some cases secondary deposits were found in the adjacent 
lymph-glands, liver, and spleen. They made many succsseful trans- 
plantation experiments, but some animals were found to be immune. In 
several instances they witnessed spontaneous resolution, the subsidence 
often being concomitant with ulceration. Dogs that recovered after 
inoculation, were found to be immune to fresh grafts. These authors 
considered the disease to be, small round-celled sarcoma. 

White 3 regarded the tumours as "warty growths," very different 
from any known form of human sarcoma ; and by Sticker 4 the condi- 
tion is described as lympho-sarcoma. 

Seligmann 5 has lately reported other instances of this malady, which 
he describes as " infective tumours " ; in one of these cases, the disease 
disseminated from the prepuce to the testis. 

It is evident from the foregoing profession of faith, that pathologists 
still lack a really satisfactory criterion for malignancy in general, as well 
as for particular varieties of malignancy. 

It is probable that growths of somewhat similar nature are common 
enough, under certain conditions, in other kinds of animals, especially in 
rats and mice. 

Of like nature with the foregoing, are the contagious papillomata of 
the mouth of dogs ; which, as shown by Penberthy 6 and others, spread 
among dogs kennelled together. This malady is also communicable by 
experimental implantation ; and, after a time, it is apt to undergo 
spontaneous resolution, such animals then being immune. 

The malady seems to have some similitude with the " sublingual 
tumour " of human nurselings, which is a papillary outgrowth, as 
described by Riga and Fede. 

Not many implantation experiments have been reported with other 
kinds of non-malignant tumours ; but Loeb 7 essayed the transplantation 
of a solid adenoma from the mamma of a rat, into other parts of the same 
animal and into other rats, with negative results ; except that in one 
case, the graft into a pregnant animal increased until young were born, 
when it quickly dwindled away. 

Lanz's 8 grafting experiments with various benign tumours, all gave 
1 " Verhandl. d. deutsche Gesellsch. f. Chir., 1895" (Twenty-fourth Congress, Berlin), 

Transactions of the Pathological Society, London, 1897, vol. xlviii., p. 310. 

British Medical Journal, 1902, vol. ii., p. 176. 

Zeits. f. Krebsforschung, 1904, Bd. i., S. 418 ; also ibid., Bd. iv., Heft 2. 

Transactions of the Pathological Society, London, December, 1906. 

Journal of Comparative Anatomy, 1898, vol. xi., p. 363. 

Journal of Medical Research, 1902, vol. viii., p. 74. 8 Op. cit. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 181 

only negative results. Mayet, 1 however, claims to have produced 
sarcoma in a dog, by the injection of a filtered solution of myoma of the 
uterus of a woman. 

It seems to me that the time has now come for clearly recognizing 
the fact, that there are many noxious agents, extrinsic as well as intrinsic, 
capable of exciting the tissue cells to proliferative activity. In the face of 
such evidence as I have already adduced, and of such additional evidence 
as I have still to supply, the dictum of Weigert supported as it is by 
Ziegler and other pathologists that irritants ab extra are incapable of 
causing formative reactions, needs modification. Borrel's researches, 2 
supported as they are by many converging indications, specially point in 
this direction ; thus he has shown, that the proliferative activity of the 
epithelial cells of cancerous tumours has many analogies in other morbid 
conditions, such as occur in molluscum contagiosum, Darier's disease, 
vaccinia, sheep small-pox (" la clavelee ") etc., to none of which the 
least suspicion of malignancy attaches. 

In molluscum, which is an epidermoidal new formation, many of the 
morphological appearances of cancer are met with, e.g., irregular epithelial 
hyperplasia with budding ingrowths, excessive keratinization etc. ; and, 
microscopically, various mi to tic irregularities, cell inclusions etc. The 
contagious nature of the malady has been noted by many observers ; 
while others have proved its transmissibility by experimental means : 
thus Pick inoculated some of the tumour contents into a boy and girl, / 
and ten weeks later, characteristic tumours developed at the seats of 
inoculation, and subsequently others formed. No one, however, has 
succeeded in isolating or cultivating any causative microbe. Marx and 
Sticker claim to have proved that the infective agent, whatever it may 
be, is sufficiently minute to pass through filters which retain ordinary 
microbes. 

It was formerly overlooked, that various noxious agents may cause 
the formation of quasi-malignant tumours in mankind and in animals, 
e.g., quasi-epitheliomatous lesions due to blastomycosis, as in cases re- 
ported by Gilchirst, Owens, Hyde Hektoen etc. ; and, in animals, such 
tumour-like new formations as are seen in coccidial disease of the rabbit's 
li ver ; and sarcoma-like tumours, due to actinomycosis and blastomycosis, 
such as Busse, Curtis, and others have recorded. The recollection of these 
conditions, will serve as a good introduction to the experimental study 
of malignant tumours, especially when we add thereto the remarkable 
instance of the infective papillomata of dogs, so often mistaken for cancer. 



Experiments with Malignant Tumours. |> \- 

During the last twenty years, an immense number of workers in th's 
field, claim to have artificially produced malignant tumours : (1) by 
inoculation of cultures of various so-called " cancer microbes " ; and 
(2) by diverse kinds of tumour-tissue grafting etc. 

1 C. R. de I'Acad. des Sci., 1905. 

2 " Epithelioses infectieuses et epitheliomas," Ann. de I'Inst. Pasteur, 1903, xvii., 
p. 81. 



182 THE NATURAL HISTORY OF CANCER 

With regard to most of these claims, supported as they are by detailed 
accounts of the histological analysis of the tumours, they only show how 
utterly unreliable such findings are, as evidence of the real nature of the 
malady in doubtful cases. 

In dealing with these claims, the need for caution is very manifest ; 
for, in this branch of pathological work, more perhaps than in any other, 
experience is apt to be deceptive and judgment difficult. 

As to the first group of experiments, their history will be recorded 
in the sequel ; l hence, all that need be noted here is, that their futility 
is now generally recognized, most of them having already passed out of 
recollection. 

It is with the second group of claims that we now have to deal ; and, 
at the outset, I may as well state my conviction, that none of them have 
scientific validity. 

Most of those who have been engaged in this kind of work, have been 
so absorbed in their own undertakings and prepossessions, that they 
have seldom been able to gauge aright the scientific value of their own 
findings, as is abundantly testified by such review of their work as I have 
previously mentioned ; and, as is still more emphatically confirmed, by 
the further examples I will now proceed to adduce. 

The evidence bearing on this subject may, for convenience of dis- 
cussion, be grouped under the^ following heads : 

(a) Grafting of human cancer into animals ; 

(b) Grafting cancer as between animals of the same, and 

(c) Of different species ; 

(d) Transmissibility of cancer from one human being to another ; and 

(e) Auto-implantation. 

(a) Grafting Human Malignant Tumours into Animals etc. 

Of the numerous attempts that have been made from time to time, 
to transmit human malignant tumours experimentally to animals 
whether by grafting, inoculating with the juice, magma etc., by intra- 
venous injection, and other ingenious methods the results have almost 
invariably been negative. 

Among the earlier experimenters, only Langenbeck, 2 Follin, 3 C. 0. 
Weber, 4 and Goujon, 5 claim each a single successful result. 

Langenbeck injected the creamy juice of a recently removed malignant 
tumour of the human humerus, mixed with defibrinated blood, into the 
femoral vein of a dog. The injection induced intense dyspnoea, which 
soon subsided ; so that a week later, the animal seemed in fairly good 
health. Subsequently emaciation set in, and the animal was killed in 
this state, sixty-three days after the injection. The post-mortem 
examination revealed several small, hard nodules, varying in size from 

Q.v. Chapter X. 

"Schmidt's Yahrbiicher d. gesam. Med.," 1840, Bd. xxv., S. 104. 
Lebert's " Traite pratique des maladies cancereuses," 1851, p. 136. 
" Chirurgische Erfahrungen und Untersuchungen," Berlin, 1859, S. 289. 
These de Paris, 1866 : " Expose de quelques faits tendant a demontrer que les 
cancers de l'homme," etc. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 183 

an almond to a lentil, at the surface of each lung ; and a similar small 
nodule in the middle of the left lung. Histologically examined, these 
nodules resembled in structure the tumour of the humerus, whence the 
juice used for injection was derived. 

Follin repeated Langenbeck's experiment by injecting into the 
jugular vein of a dog, a magma derived from a recurrent cancerous mass, 
recently removed from the axilla of a woman, whose breast had been 
previously extirpated for cancer. On the fourteenth day after the 
injection, the dog was killed ; and, on examining the body, several small 
firm nodules were found in the lungs, in the walls of the heart, and in 
the liver. These formations were seldom larger than a pin's head ; and, 
histologically, they were found to comprise " cancer cells." 

The nodules in these cases, were probably nothing but consolidating 
inflammatory lesions, around embolic tumour grafts artificially produced 
by the intravenous injections. Had more time been allowed, they would 
probably have completely disappeared. Such was actually the course of 
events, in the many similar experiments, subsequently made by Virchow, 
Vogel, Wyss, Billroth, and others. In these cases, the animals experimented 
on were not killed until several months after the injection ; when no 
trace of cancer nodules could be found in any part of their anatomy. 

The positive results of the other experimenters, are even less con- 
vincing than the foregoing. 

Dupuytren a fed dogs and other animals for considerable periods with 
human malignant tumours, but they did not acquire the disease ; and 
the dogs that Alibert caused to swallow discharge from cancerous ulcers 
etc., experienced similar immunity. Shattock and Ballance 2 have, in 
like manner, fed white rats for several months, with fresh cancers of the 
female breast, with only negative results. 

In comparatively recent times, several additional examples of this 
kind of experiment have been reported ; but, almost invariably, the 
results have been negative ; thus of the numerous attempts made by 
Sticker 3 and Hemmeter, 4 to implant human cancer into dogs, cats, guinea- 
pigs etc., all were unsuccessful. 

In judging the value of the alleged positive results, it is necessary to 
bear in mind that quasi-malignant tumours of parasitic origin to which, 
as we now know, humanity is liable may have been used, some of which 
are known to be inoculable : for instance, the quasi-sarcomatous tumour of 
the thigh, described by Curtis 5 which was due to blastomycetic infection 
was easily inoculated into various animals ; and it is the same with 
the still commoner quasi-malignant tumours due to actinomycosis (as 
shown by the experiments of Wolff and Israel), tuberculosis, and other 
infective parasitic pseudo-plasms. 

Subjoined are some examples, of the more notable of these alleged 
positive transplantation experiments. 

Into the peritoneal cavity of a white rat, Dagonet 6 injected a m&lange 

1 Oaz. Med. de Paris, 1838, p. 47. 2 British Medical Journal, 1891, vol. i., p. 567. 

3 Zeits. f. Krebsforschung., 1904, S. 413. 

4 American Journal of Medical Science, April, 1903. 
6 Ann. de I'Inst. Pasteur, 1896, t. x., p. 449. 

6 Arch, de Med. Exp., etc., May, 1904. 



184 THE NATURAL HISTORY OF CANCER 

of a cancerous lymph-gland, secondary to epidermoidal cancer of the 
penis, in saline solution. After some months, the animal began to emaciate 
progressively ; and died thus, fifteen months after inoculation. Multiple- 
nodules were then found in the omentum, spleen, and liver, which were 
of similar structure to the original human tumour. Considering the 
great procli vity of white rats, kept in captivity, to develop quasi-malignant 
tumours spontaneously, or by contagion from other rats, of which more 
anon, it seems likely that this is the explanation of the tumours found in 
this case, especially as the peritoneum was free from the disease. 
The very numerous experiments of this kind, that have been made 
by other observers, with only negative results, also point to this con- 
clusion. 

By injecting the ascitic fluid derived from a patient with colloid 
cancer of the peritoneum, into the jugular vein of a guinea-pig, Gaylord x 
found when the animal was killed three and a half weeks after the 
jnjection a small nodule in one lung, which he considered to be " adeno- 
carcinoma." Subsequently numerous other experiments of this kind 
were made, with a similar result in a few cases. In a dog thus treated, 
he found when the animal was killed ninety days after the injection 
numerous " cancerous " nodules in the liver. Subsequently Hansemann 
histologically examined the pulmonary nodule, but could find no evidence 
of its cancerous nature. In one of the above cases, the ascitic fluid was 
kept for two weeks in an incubator, before it was used for injecting into the 
jugular vein of a guinea-pig ; when this animal was killed, fifty days later, 
nodules of " beginning cancer " were found in its lungs. 

Having collected the ascitic fluid from a patient with colloid cancer 
of the peritoneum, and kept it for ten days in an incubator, Pease 2 
practised intravenous injection of this fluid into guinea-pigs ; and, in one 
case, when the animal was killed three and a half weeks later, he found a 
nodule of " adeno-carcinoma " in the lung. 

Lewin 3 claims to have transmitted human ovarian cancer to dogs : 
while Dagonet and Mauclaire 4 also claim to have transplanted human 
rectal cancer into rats. 

Many unsuccessful attempts have been made to produce leukaemia 
experimentally ; but Lowitt 5 now claims to have succeeded, by intra- 
venous injection of material from leuksemic organs into rabbits. 

By implanting into rabbits, guinea-pigs, and dogs, various human 
cancer tissues, Bosc and Vedel 6 claim to have produced "cancerous" 
nodules at the seats of inoculation. 

Herzog 7 has many times tried to produce malignant epithelial and con- 
nective-tissue tumours, in rabbits and guinea-pigs, by injecting triturated 
human material subqutaneously, intra-peritoneally, and into the anterior 
chamber of the eye, but without success ; for, although in some cases 
nodules formed at first, they subsequently completely disappeared. 

1 American Journal of Medical Science, 1901, vol. cxxi., p. 503. 
" Public Health Papers and Reports," vol. xxv., 1900. 

3 Zeits. f. Krebsforschung., 1906, Bd. iv., S. 55. 

4 Arch, de Med. Exp., 1904, t. xvi., p. 552. 

5 "Twentieth Century Practice of Medicine," 1903, vol. xxi. (suppl.). p. 571. 

6 La Semaine Med., 1898, p. 166. 

7 Journal of Medical Research, 1902, vol. viii., p. 74. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 185 

Juergens l injected into the peritoneal cavity of rabbits, a magma 
derived from a metastatic sarcoma of the human cerebral meninges. 
Three months later, one of the animals was found to have a tumour in 
its right eye. On post-mortem examination a month later, a sarcomatous 
tumour, the size of a hazel nut, was found there. The tumour teemed with 
coccidia-like organisms. This is probably a case of microbic infection. 

In another rabbit, in which bits of a myxo-sarcoma of the human 
ovary, had been implanted in the peritoneal cavity, tumours were found 
when it was killed some months later in the lungs, small and large 
intestines. These tumours also teemed with coccidia-like bodies. 

Juergens also claims to have successfully implanted into animals frag- 
ments of sarcoma, taken from a human subject three days after death. 

Some interesting implantation experiments have been made with 
human melanotic tumours. 

These were started many years ago by Goujon, 2 who injected sub- 
stances of this kind into various animals. At the seat of inoculation, he 
noted that one or more small black tumours sometimes formed. Soon 
afterwards pigment appeared in the adjacent glands ; and, at a subse- 
quent period, in more remote glands. He specially notes the great 
augmentation of the total amount of pigment which ensued after the 
injection, as if by multiplication of living pigment-producing elements. 

By injecting triturated human melanotic tumour in saline solution, s * 
into the spleen of a guinea-pig, 0. Lanz 3 found, seven weeks later, a small 
pigmented nodule in the animal's left external ear ; moreover, all the -^ 
internal organs contained a large amount of free and intra-cellular pig- 
ment, i.e., there was diffuse melanosis. 

Bosc and Vedel 4 inoculated guinea-pigs with human melanotic sarcoma &- 
material, subcutaneously and intra-peritoneally ; and so produced in > ' 
them nodules of melanotic sarcoma. 

By implanting a small fragment of a secondary melanotic sarcoma 
from a woman, at the root of the tail of a mouse, Pfeiffer 5 produced a 
melanotic tumour at the seat of implantation. He transplanted frag- 
ments of this tumour into twelve other mice, in one of which a similar 
growth developed. Even before Goujon's time Klencke (1843) claimed 
to have successfully transplanted human melanoma into horses and dogs. 

Juergens 6 had previously made many experiments of this kind ; 
thus, having implanted under the conjunctiva of a rabbit's eye, a small 
bit of recently extirpated human melanoma, a fortnight later a melanotic 
tumour had developed at th seat of implantation. 

Juergens also implanted, in the peritoneal cavity of six rabbits, y 
fragments of melanoma from the human pancreas, with the result that 
within a few weeks, each of these animals developed intra-abdominal 
pigmented tumours, with similar nodules in the pericardium and heart 
as well, in one case. 

All these new formations teemed with pigmentiferous coccidia-like 
bodies. 

1 Berlin klin. Woch., No. 15, 1895, p. 331 ; see also pp. 465 and 747. 

2 " Inoculabilite des elements pigmentaires ou melaniques," Gaz.det Htipitaux, 1867, 
p. 339. 

3 Deutsche med. Woch., May 18, 1899. * Op. cit. 

5 " Die Protozooa als Krankheitserriger," Jena, 1891, p. 204. 6 Op. cit. 



186 THE NATURAL HISTORY OF CANCER 

In this connexion it is interesting to recall, that Lancereux found the 
blood of patients affected with disseminated melanotic tumours, very 
rich in pigment-bearing elements. 

Here also reference may be made to the little-known facts about 
melano-mycosis, 1 and its experimental transmissibility .; as well as to the 
recent experiments of Charrin and Le Play, 2 who by subcutaneous and 
intra-peritoneal injection into various animals, of pure cultures of the 
fungus (Stearophora radicicola), which grows on the root of the vine, 
produced black-coloured tumours like melanomata. Bard 3 also has 
shown the parasitic nature of certain melanotic tumours. 

Fischel' s attempts to implant human melano-sarcoma into rats all 
failed ; and a similar fate befell Roux and MetchnikofFs implantations of 
the same morbid substance into the chimpanzee. 4 

With material obtained by harpooning fragments of human cancers 
and mashing them up, Dubois 5 inoculated animals subcutaneously. As 
a result, tumour-like swellings formed soon afterwards, in several cases. 

Boinet 6 inoculated a series of forty rats intra-peritoneally with fresh 
human malignant tumours ; and, a month later, one of these animals 
became paraplegic, and died thus a few days afterwards. It was then 
found to have two cancerous tumours adherent to the spine, abave the 
central tendinous part of the diaphragm, the adjacent dorsal vertebrae 
and liver being invaded, and the spinal cord compressed. Histological 
examination of these nodules showed that they comprised proliferating 
epithelial elements, similar to those of the human tumour, whence the 
material used for inoculation was originally derived. 

The other results of this series of experiments were negative ; as also 
were numerous subcutaneous implantations in various animals. 

Mayet 7 claims to have successfully transmitted human cancer to 
white rats, under circumstances which preclude the possibility of tissue 
or cell grafts being concerned in the process. Thus, by repeated subcu- 
taneous injections of a glycerine extract of aseptically macerated human 
cancer, filtered through porcelain or asbestos, he has several times pro- 
duced in these animals, after an interval of some months, " des lesions 
cancereuses epitheliales." It is of interest to remark that with dogs and 
rabbits, similar experiments yielded only negative results. 

Firket 8 implanted fragments of human sarcoma into rats ; and, five 
weeks later, in several cases, tumours developed at the seats of inoculation. 

By injections of cancer juice from human malignant tumours into 
white mice, Francotte and De Rechter 9 claim to have caused the formation 
of cancerous tumours, some months later, at the seats of inoculation. 

As we have already seen, white mice and rats are so prone to originate 
quasi-cancerous tumours spontaneously, that the causative relation of 
the injections to the tumours in these cases, is by no means evident. 

Among those who have essayed to transplant human cancer to 

1 Transactions of the Pathological Society, London, vol. xlii., 1891, p. 423 
(Delepine). 

2 G. R. de I'Acad. des Sci., 1905. 3 Lyon Mid.. 1885, t. xlviii., p. 407. 
* Butt, de I'Acad. de Med., 1903, p. 3. 5 Bulletin Med., August 16. 1896. 

6 La Semaine Med., June 13, 1894. 

7 Lyon Med., 1905, p. 1356 ; also ibid., December 11, 1904, and August 19, 1893. 

8 La Semaine Med., 1893, p. 8. 9 Bull. R. Acad. de Med. de Belgique, 1892, p. 999. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 187 

various animals, with negative results, mention may be made of Duplay 
and Cazin, Shattock and Ballance, Senn, Weigert, D'Arcy Power, Senger, 
Fischel, Wickham, Klebs, D'Anna etc. 

Shattock and Ballance x undertook many experiments to this end, 
implanting portions of quite fresh human malignant tumours into 
monkeys, dogs, rats, cats, and sheep ; but the results were always 
negative ; hence they concluded that it is impossible to transmit the 
human disease to animals. 

In two of their experiments, entire scirrhous cancers of the female 
breast were inserted into the abdominal cavity of animals, and disappeared 
after a time without leaving a trace ; in like manner, large slices of chondri- 
fying round-celled sarcoma of the humerus when similarly treated 
completely disappeared. 

Having in view the immense preponderance of negative results and 
the many sources of fallacy, to some of which I have previously referred 
I can only regard the alleged successes in this kind of experiment, as 
resting on insufficient evidence to ensure credibility. 



(b) Grafting Experiments as between Animals of the Same Species. 

It seems reasonable to suppose that implantation experiments might 
have a better chance of success, if confined to animals of the same 
species ; but, in this direction also, most experiments have proved 
abortive (Bert, Jeannel, Gratia, Senn, Kb'ster, Erbre, Doultrelepont, and 
many others). 

In comparatively recent times, however, several experimenters allege 
that they have succeeded in transmitting " cancer " from mouse to mouse, 
and from rat to rat. What is the real nature of this so-called cancer ? 

The great mistake of those who have so prematurely identified 
" Jensen's mouse tumour " with cancer is, that in making their diagnosis 
they have placed far too much reliance on histological appearances the 
fallaciousness of which has so often been demonstrated in recent times 
and far too Little on the ensemble of the indications available for 
diagnostic purposes. 

It was by following this line of fallacies that Wehr, Smith and Wash- 
bourn, and others, formerly persuaded themselves and the majority of 
pathologists, that the infective venereal tumours of dogs were examples 
of contagious inoculable cancer ; indeed, it is only lately that this wide- 1 
spread fallacy has been exploded. 

Experimental pathologists are only now beginning to recognize, 
although pathological anatomists have long been aware of it, that 
epithelial proliferations in their structural details very like cancer are 
of common occurrence in many non-cancerous conditions. 

These considerations alone should have sufficed to cause the present 
subject to be approached with the greatest caution, but the event has been 
iar otherwise ; for, the modern experimenter being a law to himself, is 
only too often quite impervious to the plainest lessons of history, even to v 
those that may be learnt from his own speciality. This narrowness of 
outlook, is the cause of the extraordinary concatenation of blunders with 
1 Proceedings of the Royal Society, London, 1890, vol. xlviii. 



188 THE NATURAL HISTORY OF CANCER 

which the history of the experimental study of cancer is cumbered ; 
indeed, if we put aside the Miinchausen creations, very little solid fact 
remains as the outcome of so much vapouring. 

, " . ^p. Now, what are the plain facts in respect to which " Jensen's tumour " 
differs in toto from cancer, or any form of human malignant tumour ? 
They are briefly these : 

The disease is highly contagious ; and the observations of many 

competent pathologists (Gaylord, Borrel, Haaland etc.), who have 

specially studied this aspect of the malady show, that when infected 

animals are introduced into cages with healthy animals, the latter take 

^ -Vthe malady as if by local contagion. 

There can be no doubt that mice kept in captivity, especially those 
confined for experimental use in scientific laboratories, which are often 
numerous and get but little hygienic attention, are singularly prone to 
epidemic outbreaks of " cancer," as signalized by Gaylord and Clowes, 1 
Haaland, 2 Borrel, 3 Loeb 4 etc. 

As long ago as 1891, Morau 5 found that mice fed with a paste composed 
of chopped-up tumour and bread-crumbs, developed the disease ; and some 
recent observations of Borrel, as to the spread of the infection through 
contaminated water, are of similar import. 

Because his experience of this occurrence has been negative, so far as 
evidence of contagion is concerned, Dr. Bashford 6 seems to think that this 
negative experience justifies him in denying point-blank the very positive 
results of the above-mentioned pathologists, which he ascribes to fallacious 
- observations, erroneous deductions, and lack of personal experience. In 
my opinion this criticism is unjustifiable, and without scientific warrant. 
Ifc is not the first mistake of this kind that Bashford has made ; for, having 
denied, as the result of his own negative experience, the positive results of 
Clowes, 7 as to the immunity of mice whose tumours had undergone 
spontaneous cure to reinoculation, he has recently had to eat his own 
words ; and, so long as this vicious kind of criticism is indulged, similar 
results may be anticipated. 

That various parasites to which mice are specially prone, such as 
sporozoa, are capable of originating contagious quasi-malignant growths, 
we know from the researches of Borrel and others. Yet these " infective 
epithelioses " are just as different from cancer, as are the coccidial tumours 
of the rabbit's liver, with which they are really analogous. 

As Twort 8 has. lately indicated, many cases of so-called " cancer " in 
mice, are commonly associated with invasion of the part by sarco-sporidia 
(Miescher's cylinders) ; while the extraordinary facility with which this 
/ sporozoan muscle parasite can be transmitted from mouse to mouse, by 
feeding with contaminated muscle, has been well demonstrated by 
T. Smith. 9 

1 British Medical Journal, 1906, vol. ii., p. 1555; also Journal of the American 
Medical Association, 1907, p. 15. 

Ann. de I'Inst. Pasteur, 1905, vol. xix., No. 3, p. 156. 

C. R. Soc. de Biologie de Paris, 1905, p. 770. 

Univ. Penn. Med. Butt., U.S., April, 1907. 

C. R. Soc. de Biologie de Paris, 1891, t. iii., pp. 289, 721, and 801. 

Lancet, 1907, vol. i., p. 802. 

British Medical Journal 1906, vol. ii., p. 1548. 

Transactions of the Pathological Society, London, 1907. 

Journal of Experimental Medicine, May, 1905, p. 429. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 189 

Some recent observations by Borrel x seem to show that certain of 
these " Jensen tumours " are formed round vermiform parasites, which 
end their existence thus, after having lived for a time in the animal's 
blood ; and the experiments of Rouget have shown that mice and rats are 
very prone to trypanosome infection. 

In this connexion, it is also of interest to note, that Borrel, Gaylord and 
Calkins have often found the blood of these tumours teeming with 
parasitic spirochaetae. 

In the present state of this inquiry, it would be premature to speculate 
as to the precise value of these significant finds ; but they seem to point 
to distinct causative agents for these pseudo -plasms. 

Since this was written Jacobs and Geets, by inoculating mice and T- ' 
rats with cultures of Doyen's Micrococcus neoformans, claim to have 
produced thus similar local and general cancerous tumours. 

By exposing pieces of " Jensen's tumour " to the very low tempera- 
tures generated by liquid air, Moore and Walker 2 lately found that 
these tumours nevertheless retained their power of inoculability. It is 
well knowri that many microbes and spores retain their vitality even 
after exposure to such low temperatures, which kill the tissue cells. 
From this it may be inferred, that the infective agent in these tumours- 
is of parasitic origin. 

There is no evidence as to the occurrence of contagion, such as is met 
with in these mice pseudo-plasms, in any form of human cancer at least, 
not outside the Miinchausen sphere ; but, in the contagious venereal 
malady of dogs, analogous conditions are commonly met with. ' ; Jensen's 
tumour " is readily transmissible by implantation to other mice, the 
proportion of successful experiments often being as high as 50 per cent. 
indeed, Morau using only closely related animals succeeded in 80 per 
cent, of his experiments. 

No such property is ever manifested by human cancer ; but, with the 
contagious venereal pseudo-plasm of dogs, similar conditions obtain. 

A considerable proportion of white mice are immune to the contagion 
of this disease, whether in its spontaneous or experimentally determined 
form ; and sometimes whole families manifest this peculiarity. The same 
phenomena have often been noted in the contagious malady of dogs. 

Moreover, " Jensen's tumour " fairly often undergoes spontaneous 
resolution ; and the cured animals are then immune to further contagion, 
giving only negative results when inoculated, as Gaylord and Clowes have 
specially pointed out. With human malignant tumours, no such spon- 
taneous curability has ever been scientifically demonstrated ; but, with the 
venereal pseudo-plasms of dogs, this phenomenon is of common occur- 
rence. 

" Jensen's tumour " is circumscribed and easily enucleable, the tissues 
of the host forming no part of it ; moreover, the latter do not acquire 
cancerous properties, nor do they become interpenetrated by processes 
of the pseudo-plasm; and, besides this, "Jensen's tumour" generally 
causes no cachexia. 

1 C. R. Soc. de Biologic de Paris, 1905, p. 770 ; also British Medical Journal, 1906,. 
vol. ii., p. 392. 

2 Lancet, 1908, vol. i., p. 226. 



190 THE NATURAL HISTORY OF CANCER 

Finally, according to Apolant and Ehrlich, 1 " Jensen's tumour " in the 
course of experimental transmission often changes its anatomical type 
from the epithelial to the sarcomatous etc. ; and Morau found, under 
similar circumstances, that its physiological type also changed, with 
corresponding alteration in its power of inoculability. Lately from 
" adeno-carcinomata," inoculable " sarcomata," and " sarco-carcino- 
mata " of mixed type, have been obtained ; and these latter have again 
produced " pure sarcomata " ; while these malignant formations have 
been found to revert to " benign adenoma." 

In all of these vitally important respects, which, taken together, are 
crucial for diagnostic purposes, " Jensen's tumour " whatever its real 
nature may eventually turn out to be is totally unlike any form of 
human cancer. 

jQn the other hand, like the venereal malady of dogs, " Jensen's 
tumour " can usually be successfully grafted into other animals of similar 
species. 

Another feature in regard to which the two maladies present a certain 
resemblance is, that in both 'secondary disseminative lesions occasionally 
result ; so that, in this respect, " Jensen's tumour " resembles certain 
artificially produced pseudo-plasms such, for instance, as those San- 
felice, O. Schmidt, Curtis, Busse, and others produced, by inoculating 
animals with certain pathogenic yeasts. 2 

It was Morau, 3 in 1891, who first specially directed attention to this 
so-called cancer (" epitheliome cylindrique ") in mice ; and subjected the 
malady to experimental tests. 

The original tumour developed spontaneously in the subcutaneous 
tissue of the axilla of a captive white mouse. It was easily enucleable, 
non-adherent to contiguous structures, and caused no disturbance of 
the animal's general health. A portion of this -tumour, immediately after 
its aseptic ablation, was by trituration reduced to a magma, which was 
forthwith injected into the subcutaneous tissue of a series of other white 
mice. About three months afterwards, it was noticed that nearly all 
the injected animals presented similar tumours at the seats of inoculation 
and elsewhere, which subsequently slowly increased in size. One of 
these tumours was then enucleated, and from it fresh magma was 
prepared, with which another series of mice was injected ; and these 
also, after a similar interval, acquired the disease. Experiments of this 
kind were successfully continued through several generations. 

It is noticeable that the animals used for these experiments were all 
of the same strain, closely inter-related, and had all lived in the same 
cages. This no doubt explains the very large proportion over 80 per 
cent. of successful implantations ; for, when animals of foreign strains 
were used, the proportion of successful inoculations was much less. In 
subsequent experiments of this kind, Morau found that when the malady 
had been artificially transmitted through a considerable number of 
generations, the inoculability of the tumour markedly diminished. 

1 Berlin, klin. Woch., 1905, xlii., S. 871 ; ibid., 1906, No. 2 ; also Arbeit, aus k. Inst. 
f. exp. Therap. z. Frankfurt-a.-M., 1906, S. 65 and 77. 

2 For details, vide Chapter X. 

3 C. R Soc. de Biologic, Paris, 1891. t. iii., pp. 289, 721, and 801 ; also Arch, de Med. 
exp., etc., September, 1894, t. vi., p. 677. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 191 

Morau seldom noticed dissemination, except after traumatisnT< 
affecting the edge of the tumour. 

No cultures could be obtained from any of the many tumours 
examined, nor could any microbes be discriminated. 

Attempts to transplant the malady into other animals than mice failed. 

Jensen l did little more than repeat, extend and popularize Morau's 
experiments, which in the intervening decennium had been forgotten. 
From a small subcutaneous tumour on the back of a white mouse, whose 
histological structure resembled that of tubular cancer, he took pieces 
and brayed them in a mortar with physiological salt solution. Small 
quantities of this melange were injected subcutaneously into a series of 
white mice, with the result that tumours, like the original, developed at 
the seat of inoculation in most cases. Even by the fourteenth day after 
injection, small nodules were visible ; and, in the course of some months, 
quite large tumours had formed sometimes as large as, or even larger 
than, the affected mouse. The tumours were transmitted in this way 
through over twenty generations of mice, about half of those inoculated 
producing tumours. Some animals, and even entire families, were 
immune ; and those in whom first injections, failed, yielded negative 
results to further injections. 

From white mice the disease was only occasionally and with difficulty 
transmitted to the grey kind ; and negative results followed all attempts 
to produce it experimentally in white rats, guinea-pigs, rabbits, goats 
and ducks. 

Jensen regarded his experimentally produced tumours as implantation 
grafts, derivatives of the transplanted tumour cells ; and he could neither 
detect any microbes in the tumours, nor get any cultures of such. 
Metastatic tumours were not noticed. 

Borrel 2 performed many similar experiments with like results. In 
tumours of some duration, he found metastases very common, especially 
in the lungs. These he determined arose from graft-like cellular emboli, 
detached from the primary tumour, which reached the lungs by the 
bloodvessels. He demonstrated many tumour grafts of their kind, 
within the pulmonary bloodvessels. 

Haaland 3 and Bashford 4 have also made many confirmatory experi- 
ments of this kind ; but without otherwise adding to our knowledge of 
the malady, the real nature of which has yet to be determined. 

In a communication published subsequently to the one above cited, 
Borrel 5 has reported some interesting particulars as to these tumours. 
In the centre of each nodule he has commonly found marked indications 
of active phagocytic processes, characterized by the presence of large 
mono-nucleated cells, greatly hypertrophied, vacuolated, and " bourrdesde 
detritus de toute sorte." In the vicinity thus characterized, numerous large 
blood sinuses abounded. Around the central area the epithelial tubules, 
which constituted the real tumour, were disposed in a radiating manner. 
These phagocytic areas, he considers due to small vermiform parasites, 

1 Hospitalstidente, No. 19, 1902; also Nos. 21 and 22. 1903: and Zznt. f. Bakt., 1903, 
Bd. xxxiv., No3. 1 and 2. 

2 Ann. de I'Inst. Pasteur, 1903, vol. xvii., p. 81. 3 Ibid., 1905, vol. xix., p. 156. 

4 Scientic Reports of Cancer Research Fund, 1904 and 1905. 

5 C. E. Soc. de Biologie de Paris, 1905, t. i., p. 770. 



192 THE NATURAL HISTORY OF CANCER 

which end their existence here after having lived for a time in the animal's 
blood ; and in this connexion it is interesting to note, that he has often 
found spirochaetae in the blood sinuses of these tumours, sometimes in 
immense numbers, as also has Ehrlich. 

Loeb, 1 like Apolant and Ehrlich, also claims to have artificially pro- 
duced carcinomatous and sarcomatous tumours in Japanese mice, by 
inoculating them with carcinomatous growth, derived from the sub- 
maxillary gland of a Japanese mouse. 

Like mice, rats are also subject to a quasi-malignant kind of tumour, 
which is contagious, transmissible by implantation, and in other respects 
much resembles the above-described malady of mice. 

Hanau 2 was the first to describe and experiment with this pseudo- 
plasm. He injected material from an " epidermoidal cancer " of the 
vulva of a rat, into the tunica vaginalis testis of two other rats : one of 
these died seven weeks later, with diffuse nodular " cancer " of the 
peritoneum ; the other was killed eight weeks after inoculation, when two 
" cancerous " nodules were found, one in the adrenal, the other in the 
gubernaculum testis. With material from one of these nodules, a third 
rat was injected ; and when it was killed, three months afterwards, it 
presented a tumour at the seat of injection, as well as diffuse nodular 
growths throughout the peritoneum, and in the posterior mediastinum. 
All of these tumours were histologically of similar structure to the original 
vulvar tumour. Hanau considered that these results show, " successful 
grafting of tumour tissue." 

Eiselsberg 3 grafted portions of a " fibro-spindle-celled sarcoma " from 
the back of one rat, into the peritoneal cavity of two other rats : in one of 
these a large pseudo-sarcomatous tumour of the peritoneum developed, 
of which the animal died, five months after the implantation. In its 
histological structure, this latter tumour resembled the original. 

Velich 4 transplanted portions of a " periosteal sarcoma " of the femur 
of a white rat, into series of other rats, through nine generations ; and, at 
the seat of implantation, a tumour generally formed, which structurally 
resembled the original tumour. In one instance he succeeded in thus 
transplanting a tumour fragment, twenty-four hours after its removal. 
After several generations of successful transplantations, the power of the 
grafts to grow underwent great diminution, or was altogether lost. 
Uninoculated rats kept in the same cage with their inoculated congeners, 
developed similar tumours. Disseminative tumours were not seen in any 
of these inoculated animals. Injections with tumour juice, from which 
the cells had been removed by filtration, gave only negative results. 

Loeb, 5 with material derived from an " adeno-cystic sarcoma " from 
the thyroid region of a white rat, made a series of transplantations into 
other white rats chiefly into the subcutaneous tissue, and into the 
peritoneal cavity ; and, in most cases, at the seat of implantation, a tumour 
similar in structure to the original resulted. Local disseminative 

1 Penn. Univ. Med. Bulletin, July, 1906, p. 113 

2 Corresp. Bl. f. schw. Aerzte, 1889, No. 11, S. 334. 

3 Wien. klin. Woch., 1890, Xo. 43, S. 927. 
* Wien. med. Blatter, 1898, Nos. 45 and 46. 

8 Journal of Medical Research, 1902, vol. viii., p. 46 ; also ibid., vol. vi., p. 28. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 193 

nodules were often seen, as well as contact implantation, and even distant 
dissemination. In one case, after excision, the disease recurred locally, 
with dissemination in distant parts. In a few cases he succeeded in 
producing similar pseudo-plasms, by injecting the fluid contents of the 
tumour cysts, which contained cellular elements ; but, after these had been 
removed by filtration, the injections were always negative. In a fair 
number of cases the rats used proved to be quite immune. Several 
experiments were made to determine how long, after removal, the grafts 
would maintain their inoculability ; and, by keeping them on ice, they 
were found to be effective even after five days' exposure. 

Attempts to implant the disease into white mice, guinea-pigs, rabbits, 
and other animals, all failed ; but, in two cases, he succeeded in trans- 
mitting it into a hybrid of a white and grey rat. 

In no case could any microbes be detected in the tumours ; hence, 
Loeb concluded, that the latter were derived from the transplanted cells. 

Herzog x got similar results in a series of over fifty implantations, 
comprising eight generations. Fluid extracted from these tumours, and 
made ceU- and microbe-free by special filtration, when injected never gave 
a positive result. Attempts to implant the malady into rabbits all failed. 

Flexner and Jobling 2 have also successfully implanted mixed-celled 
sarcoma of the vesicula seminalis of a white rat, into other white and 
grey rats, with the formation of metastases in several cases. 

Loeb queries : " Are these growths sarcomata or granulomata ?" and 
he decides for the former ; but to me it seems, for reasons previously 
mentioned, that the ensemble of this malady, like the similar affection 
of mice, is totally unlike any known form of human malignant tumour. 

A few other examples of the alleged successful outcome of this kind of 
implantation still remain to be mentioned. 

Thus, in the course of attempts to transmit cancer from dog to dog, 
Mathis, 3 after many failures, claims a single success. 

In this case, having injected material from " thyroid cancer " of the 
dog, into the same part of another healthy dog, a tumour developed at the 
seat of injection ; which, in the course of three months, attained the size 
of a pigeon's egg. Histologically this tumour resembled the original one. 

In like manner^ Arloing and Tripier 4 succeeded in transplanting a 
graft of mammary "cancer" from one dog to another; and Novinsky 5 
grafted bits of an epithelial alveolar tumour from the nose of one dog, 
into the subcutaneous tissue of another dog the grafts growing into 
tumours like the original, in two out of forty-two implantations. Lately 
Bashford 6 has reported similar results. 

Goujon, 7 having grafted epithelial cancer from one guinea-pig into 
another, maintains that the latter presented at the seat of implantation 
an almond-sized tumour, together with cancerous nodules in the viscera, 
when it was killed fifteen days after the operation. 

Journal of Medical Research, 1902, vol. viii., p. 74. 

Cent. f. allgem. Path. u. path. Anal.. April 15. 1907. 

Rev. des Maladies Cancereuses, October, 1896, p. 16. 

Lyon Med., May 26, 1895, p. 119. 

Cent. f. med. Wiss., 1876. 

British Medical Journal, 1906, vol. ii., p. 1554. 

Op.cit. 



194 THE NATURAL HISTORY OF CANCER 

(c) Grafting Experiments as between Animals of Different Species etc. 

Notwithstanding alleged instances to the contrary, the transmission of 
cancer from one animal to another of a different species, has never been 
definitely proved. 

Doultrelepont x failed to transplant grafts of cancer from the mamma 
of a bitch into guinea-pigs and rabbits ; and most experimenters have 
failed to transmit the so-called " cancer " of mice and rats to other 
animals of different species. 

I have previously referred to the negative results of Dupuytren's and 
Shattock's experiments, of feeding dogs and other animals with human 
malignant tumours. 

Here passing mention may be made of certain alleged examples of 
the transmission of cancer from human beings to animals, or vice versd, 
by accidental contagion : for instance, Hyatt has reported the transfer 
of melanotic sarcoma from the horse to man ; Gross that of cancer from 
domestic animals to man ; Kuhn the case of a woman, who inoculated 
her finger with cancer while tending a cancerous cow ; Juergens the 
transfer of epithelioma from a fowl to a man's finger ; Budd the case of 
a pet dog, who contracted cancer of the tongue, from licking his master's 
cancerous lip ; Bosc, the transfer of epithelioma from a trout that had 
been eaten raw to a young man's tongue, wounded at the time by the 
spines of the fish etc. 

According to Noel, even certain tree tumours (" arboreal cancers "), 
may by contagion communicate the malady to human beings and animals ; 
while Behla considers that the cabbage parasite (Plasmodiophora brassicce) 
is equally potent in the same direction. 

Wasps, bugs, fleas, and flies, have all been regarded as infective agents 
in this sense ; and Behla considers that the peculiar local distribution of 
cancer at Luckau, is due to the agency of contagion conveyed by dogs, 
cats, rats, mice etc., besides the uncooked cabbages, radishes, water- 
cresses with other vegetables, and the dirty water. 

I have mentioned these items, not that any present credibility attaches 
to them, so far as I can see ; but because they ought to be in the naturalist's 
mind, when considering this aspect of the subject. 

(d) The Transmission of Cancer as between Human Beings. 

If cancer could be proved to be an inoculable contagious malady, 
the question as to its causation would be greatly simplified, in favour of 
extrinsic factors ; but, so far as we have hitherto examined this question, 
no reliable evidence of contagion has been forthcoming. 

Interest, of course, centres especially as to the evidence of contagious- 
ness between human beings ; and this is the aspect of the question to 
which I now propose to invite attention. 

Even as far back as the middle of the seventeenth century, there 
were those who believed that cancer was communicable by direct con- 

1 Arch. f. path. Anat., 1869, Bd. xlv., S. 501. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 195 

tagion ; and, in support of this belief, the case of a woman with ulcerated 
cancer of the breast, who is said to have communicated the disease to her 
three sons who slept with her, is instanced by Zacutus Lusitanus (1649). 
A later author of this period, Nicolaus Tulpius (1672), in support of the 
same thesis, has related the case of an elderly lady with ulcerated cancer 
of the breast, who is also said to have communicated the malady to her 
servant and nurse. Even as late as the middle of the eighteenth century, 
cancer patients were refused admission into the Hotel Dieu at Reims, 
on account of the supposed contagiousness of the malady. 

In opposition to these fanciful conceptions, I can appeal to my eight 
years' experience at the Middlesex Hospital, where although I was 
daily in the cancer wards I never noticed a single fact that could possibly 
be construed as evidence of the communicability of malignant disease 
from one human being to another ; but I noticed many indications 
which seemed clearly to imply, that the disease was neither infectious 
nor contagious. At that time, the special wards were packed with 
patients in advanced stages of cancer, mostly of the breast and uterus, 
in a state of ulceraticji. There were no day-rooms for these patients ; 
they lived and died in the same wards. No sooner was one dead, than 
her place was taken by another. The crowding was great ; yet, during 
a period of twenty years, not a single instance is known in which a nursing 
sister, probationer, nurse, ward-servant, surgeon, student, or anyone 
engaged in attendance on the cancer patients, ever acquired the disease. 
The nursing-sister in charge held her office for over a quarter of a century, 
but she was never affected. 

Among these cancer patients were many who had been inadvertently 
admitted, with various chronic ulcerative affections of a non-cancerous 
nature ; some of these lived for years in the cancer wards, but none of 
them ever took the disease. 

Many supposed examples of the transmission of cancer from one human 
being to another have from time to time been recorded (Budd, 1 Guelliot, 2 
Bosc, 3 Guermonprez, 4 Cabot, 5 Fabre, 6 Behla, 7 Boas, 8 MacEwen, 9 and 
others) ; but, the evidence adduced as to contagion in these cases, is of 
such a flimsy and obviously unreliable nature, as to absolve me from the 
necessity of detailed refutation. 

On the other hand, besides such items as I have previously mentioned, 
there is some strong evidence as to the non-contagiousness of the disease 
between human beings, which I will now proceed to relate. 

The attempts made in Paris at the Hopital St. Louis, early in the 
nineteenth century, by Alibert, 10 Biett, and others, to inoculate them- 

1 For a series of cases, vide the Lancet, 1887, vol. ii., pp. 727, 888, 919, 986, 1091, 
1 145, etc. I regard these simply as highly exceptional coincidences. 

2 Gaz. des Hdpitauz, 1892, No. 129, p. 1209; also L' Union med. du Nord-Est, 1891, 
xv., p. 106 et seq. 

3 "Le Cancer," Paris, 1898. 

* Butt. Med., March 11, 1896. 

6 Boston Medical and Surgical Journal, 1901, vol. cxliv., p. 471. 

6 Thesede Lyon, 1892. 

7 Deutsche med. Woch., June 27, 1901. 

8 Verhandl. d. XVIII. Cong. f. Med., 1900, S. 374. 

9 Glasgow Medical Journal, 1886. 

10 " Description des Maladies de la Peau observees a 1'Hopital St. Louis," 1806, p. 118. 

132 



196 THE NATURAL HISTORY OF CANCER 

"/selves and their pupils with the disease, were uniformly unsuccessful. 
In modern times, Senn * implanted the fresh pulp of a recently removed 
cancerous gland into the subcutaneous tissue of his forearm, with a 
negative result ; and, in like manner, ended Wickham's attempt to inocu- 
late himself with tissue from a case of " Paget's disease " of the breast, 
associated with cancer. 

Notwithstanding the frequency with which surgeons and medical 
men are exposed to contagion, in the ordinary course of their professional 
duties, not a single well-authenticated instance has been recorded, in 
which the disease has been acquired in this way. 

Of the thousands of persons habitually engaged in attendance upon 
the victims of this disease, how few have ever been similarly affected ! 

The United States Census Report, for 1900, 2 having shown a high 
death-rate from cancer, among nurses and midwives, as compared with 
occupied females in general, the attempt has been made to utilize this 
item, as evidence of contagion ; but, besides the need for caution in dealing 
with the statistics of this country owing to their peculiar mode of col- 
lection etc., as mentioned in a previous chapter, which make these data 
particularly unsuitable for determining a question of this kind, it is also 
necessary to notice the great disparity in age distribution, which is alone 
sufficient to entirely account for the diversity in cancer proclivity, the 
majority of nurses and midwives being very much older than most 
domestic servants, who constitute the largest class of employed females ; 
besides, the total number of deaths from all causes (1,330) in this class, 
and of cancer deaths (98), is much too small to enable reliable death-rates 
to be calculated. In short, these sources of fallacy render this item, 
quite worthless as evidence of cancer contagion, even if it could other- 
wise be properly employed for such a purpose. 

In matters of this kind, naturally occurring experiments are often far 
more conclusive, than those made under artificial conditions, with their 
numerous sources of fallacy. " Sadly strange as it may seem," says 
Matthews Duncan, " there is scarcely any disease, however formidable or 
however loathsome, in spite of which sexual intercourse and conception 
may not take place." This is strikingly true of uterine cancer, which is 
far more frequently complicated with pregnancy than is generally believed 
and, in the earlier stages of the disease, no doubt the sexual appetite is 
increased, and sexual intercourse is of common occurrence. 

In proof of this, it may be mentioned that Noble 3 had no difficulty 
in collecting records of 166 cases of pregnancy complicated with uterine 
cancer, published during the decennium 1886-1895 ; and it would be easy 
to add to this list. Cohnstein 4 has reported a remarkable series of 
cases, in which more than a single pregnancy was known to have 
taken place, during the course of uterine cancer. I know of instances of 
. pregnancy having occurred after amputation of the cancerous cervix, 
and after curettage for the same. 

1 Journal of the American Medical Association, April 28, 1906, p. 1255. 

2 Vol. iii., part i., p. ccxcviii, etc. 

3 American Journal of Obstetrics, etc., February, 1896, p. 283. 
* Arch. f. Gyn., Bd. v., S. 366. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 197 

Yet, in spite of these facts, I am not aware of a single well-authenti- 
cated case of cancer of the penis acquired in this way. 

Of 134 men with cancer of the penis, tabulated by Demarquay, 1 only 
one had a wife with uterine cancer. Bossi, 2 who has recently reinvesti- 
gated this important subject, has arrived at a similar result : of 180 
husbands known to have had marital relations with wives the subjects 
of uterine cancer, not a single one had acquired the disease. 

In like manner, Bayle many years ago reported that, having had 
under observation a considerable number of men, who had habitually 
maintained marital relations with wives known to be affected with 
uterine cancer, not one ever contracted the disease. 

The comparatively few cases, in which cancer of the uterus and penis 
have coexisted in husband and wife is so small, as to deprive them of all 
value as evidence of contagion. It accords with this, that cancer of the 
penis is a rare affection, while uterine cancer is exceedingly common ; 
thus, in 1900, 3,679 women died of uterine cancer in England and Wales ; 
but, only 100 men died of cancer of the penis. 

Among the forty-three cases of this conjunction collected by Behla 
and Guelliot from various sources, is one reported by Tross, in which 
the penile disease is said to have consisted of structures identical with 
those of the uterine malady glandular cancer of the cervix. Referring 
to this case, Dr. Brand 3 says : "It alone is sufficient to prove that trans- 
ference of cancer ceUs occurred that cancer is therefore contagious." 
When such supreme importance is attached to a particular case, it surely 
is not too much to ask, that all the details relating thereto shall be publicly 
set forth, and submitted for verification, to the scrutiny of some com- 
petent professional tribunal ; in the absence of any such details and 
impartial scrutiny, I shall perhaps be pardoned if I decline to accept 
the interpretation of the histological appearances in the sense alleged. 

Again, the children of cancerous mothers do not acquire the disease, 
even when the placenta, uterus, or other part of the genital tract is the 
seat of the malady. Moreover, mothers with cancer of the breast have 
often suckled their infants with the diseased organ, without transmitting 
the malady to their offspring. 

Thus, there is every reason to believe that cancer cannot be trans- 
mitted from one human being to another ; and that it is, in fact, essentially 
a non-contagious malady. 

(e) Auto-Implantation. 

Several instances of the apparently successful auto-implantation of 
malignant tumours, in human beings, have now been reported. 

Hahn, 4 for instance, having removed some small cancerous nodules 
from the skin of a woman with recurrent mammary cancer, implanted 
them into small wounds made in the skin of the mammary region, on the 
opposite side of the body. In the course of two months, these grafts 

1 " Mai. Chir. du Penis," 1876. 

2 Oaz. degli Osped., April 13, 1902. 

3 Quarterly Medical Journal, May, 1903. 

4 Berlin, klin. Woch., 1888, Xo. 21, S. 413. 



198 THE NATURAL HISTORY OF CANCER 

increased to the size of peas ; and, when the patient died with general 
metastases some weeks later, they were as large as cherries their histo- 
logical structure resembling that of the primary breast tumour. 

Cornil * has reported two similar cases. In one of these a fragment of 
cancer (6piiheliome tubuU), taken from the recently removed breast of 
a woman, was implanted into the opposite breast ; where, in the course 
of several weeks, it grew into a small tumour. In the other case, a fibro- 
spindle-celled sarcoma having been removed from the female breast, a 
fragment of this tumour was implanted into the opposite breast ; where, 
in the course of two months, it attained the size of an almond. The 
implanted tumour was then excised ; and, histologically examined, it 
proved to be of the same structure as the original. 

At least two other surgeons are said to have repeated these experi- 
ments, with similar results. 

If we accept this evidence as conclusive, what has been accomplished 
amounts to the artificial production of metastasis. 

In a somewhat similar experiment by Senn, 2 in which a fragment cut 
out from a cutaneous cancer of a man's leg, was inserted into another 
part of the same leg, no growth subsequently ensued ; and, by the end of 
a month, all traces of the graft had completely disappeared. 

I have found very few experiments on record, as to the auto -implanta- 
tion of cancer in the lower animals : Senn's 3 attempts on a dog, affected 
with sarcoma of the lower jaw, failed ; but, with the so-called " cancer " 
of rats and mice, successful auto-implantations have been made. 

Some weighty items of evidence as to the auto-inoculability of cancer 
come from clinical sources. 

In a considerable number of cases it has been observed, that when 
cancerous growths have remained for some time in contact with eroded, 
epithelial-covered surfaces, the latter have at length become cancerous, 
as if by direct implantation. 

Cripps 4 has related the case of a woman, with extensive cancerous 
ulceration of the left mammary region ; who, being unable to put on any 
dress, had kept her arm bent at a right angle in constant contact 
with the disease for several months. In consequence of this, the skin 
in the vicinity of the elbow became the seat of a cancerous ulcer, several 
inches in diameter. 

A somewhat similar case has been previously recorded by De Morgan. 5 

He says, " My colleague, Mr. Shaw, attended a woman whose pendu- 
lous breast the seat at its most dependent part of ulcerated cancer 
rubbed against the skin of the thorax. At the point of contact, a circular 
patch of cancerous ulceration (the size of a florin) took place, the 
intervening skin between this and the fold of the mamma remaining 
healthy." 

A. Williams, 6 in a woman aged sixty, has reported the spread by 

1 Butt, de I'Acad. de Med., 1891, No. 25 ; also Le, Progres Med., 1888, Nos. 21 and 27. 

2 "Surgical Bacteriology," 1889, p. 262. 

3 Op. cit., p. 261. 

4 Transactions of the Pathological Society, London, 1881, vol. xxxii., p. 111. 
" On the Origin of Cancer," London, 1872. 

6 British Medical Journal, 1887, vol. ii., p. 1369. 



THE EXPERIMENTAL STUDY OF CANCER GENESIS 199 

" contact infection," of an ulcerating cutaneous epithelioma of the inner 
part of one thigh, to the corresponding part of the opposite thigh. 

Examples of the spread of cancer by " contact implantation," from 
the uterus to the vagina, have been related by Thorn, 1 Czempin, 2 Fischer, 3 
Russell, 4 and others. 

One of Thorn's patients, a multipara aged forty-six whose uterus 
had been deflected to the right, where it had become fixed in its faulty 
position by adhesions subsequently developed cancerous " cauliflower 
excrescence " of the portio. Owing to the faulty position of the uterus, 
the diseased portio was constantly in contact with the left side of the 
vagina, at a considerable distance from the fornix. In this position 
papillary cancer developed, which fitted the similar growth on the 
portio, " like a saucepan-lid." Elsewhere the vagina was free from 
disease. 

Niebergall, Winter, Pfannenstiel and Leopold have described cases, 
in which the primary outbreak of the disease in the corpus uteri, had 
been followed by the appearance of similar disease in the cervix ; which 
they ascribe to inoculation, by contact with the primary cancerous 
polyp, or with debris given off from it. 

In like manner, instances have been noted by Hamburger, 5 Walter 
and others, of the spread of cancer from one vulva to the other, both the 
tumours being of the same histological structure. 

In various other parts of the body, facts of similar import have been 
reported, e.g., from one lip to another (Bergmann), from one vocal cord 
to another, from one eyelid to another (Vennemann), from the tongue 
to the adjacent cheek (Liicke), from the visceral to the parietal pleura, 
and likewise from the visceral to the parietal peritoneum etc. 

I have seen several examples of this kind, especially in the mouth and 
bladder. 

Klebs 6 has met with instances in which cancer of one part of the 
alimentary tract, has been followed by the development of cancerous 
nodules of similar structure at other parts lower down, as if by the im- 
plantation there of detached fragments ; e.g., (a) ulcerated epithelioma 
of the oesophagus, with two small nodules of similar structure below the 
cardia ; (6) ulcerated epithelioma of the mouth, with a tumour of similar 
structure in the large curvature of the stomach ; (c) epithelioma of the 
dorsum of the tongue, with a similar tumour in the large curvature of the 
stomach. 

Fiitterer 7 has lately published another case of this kind, and refers 
to six others. 

Moxon 8 and Ebse 9 have described the spread of the disease from the- 
trachea to the lungs, in a similar way ; while Dickinson saw numerous 
discrete growths form in the peritoneum, in consequence of the rupture- 
of a cancerous lumbar gland, which shed numerous detached particles 

Cent. }. Qyn., No. 10, 1894. 2 Zzits. f. Oeb. u. Qyn., Bd. xvi., Heft 1. 

Cent. f. Qyn., 1891, S. 549. * American Journal of Obstetrics, etc., vol. i., p. 293, 

Med.-chir. Rundschau, 1892, No. 12. 

Handb. d. path. Anat., Bd. i., S. 190. 7 Medicine,, 1902, vol. viii., p. 177. 

Transactions of the Pathological Society, London, vol. xx., p. 18. 

Cent. f. CUr., 1884, No. 48 (cited by Kraske). 



200 THE NATURAL HISTORY OF CANCER 

into the peritoneal cavity. Schenk has seen perforated gastric cancer 
spread in this way to the ovaries and uterus. 

Another important class of cases, in which implantation plays a leading 
part, comprises what I am in the habit of calling post- operative cancers. 

Thus, Courtin, 1 Reinecke 2 and others, have noted the frequency 
with which, after tapping for ascites due to cancerous disease, the wound 
track itself, became cancerous ; as if through implantation in it of can- 
cerous elements, conveyed there by the ascitic fluid. 

Nicaise has also seen sarcoma supervene in the track of a punctured 
wound, made through the abdominal wall, into a uterine sarcoma, under 
the supposition that it was a cyst. 

After the extirpation of malignant tumours, the resulting wound may 
not infrequently be grafted with the disease in this way ; thus Schopf 3 
reports that, having had to make lateral incisions into the vagina and 
vulva, during the course of vaginal hysterectomy for cancer of the uterus, 
these incisions subsequently became cancerous, as if from contact infec- 
tion. Leopold and others have had similar experiences. 

In other parts of the body the same thing has often been noted ; 
thus, Lawrie 4 has described a case in which, during exploratory lapar- 
otomy for cancer of the sigmoid colon, he removed a ruptured can- 
cerous gland, with his fingers ; fourteen months later a cancerous nodule 
appeared in the upper part of the laparotomy scar, owing to some fragment 
of the cancerous gland having been implanted there during extraction. 5 

The by no means rare occurrence of this kind of accident, after supra- 
vaginal amputation of the cancerous uterus by the abdominal route, and 
after many abdominal operations, is, I think, riow beginning to be 
generally recognized. 

Indeed, there are good reasons for believing, that eroded surfaces may 
be infected through contact even with the discharge from cancerous 
ulcers etc. ; and many surgeons now admit the traumatic dissemination 
of the disease, through the inoculation of wounds by the escape of " cancer 
juice " during operations. 

Hence, care should be taken to avoid cutting into malignant neo- 
plasms during their removal ; for, such is the great tenacity of life and the 
wonderful proliferative power, of even the most diminutive fragments of 
cancer, that when left behind they only too often constitute fresh 
centres of disease. 

In view of such considerations as the foregoing, even the extraordinary 
examples of auto -inoculation reported by Schimmelbusch and Kaufmann, 
cannot be summarily dismissed as being altogether improbable : the 
former states that a man who was in the habit of handling his cancerous 
ear, transmitted the disease to his lip, through the medium of his finger- 
nails ; while the latter relates the case of a man with epithelioma of the 
hand, who conveyed the disease to his eyelid, by continuously rubbing 
the part with the diseased hand. 

1 C. R. 7"*.. Cong, de Chir. Francaise, 1895. 

2 Arch. /. path. Anat., 1870, Bd. li., S. 391. 3 Wien. med. Woch., 1891, No. 45. 

4 British Medical Journal, 1906, vol. i., p. 198. 

5 For other instances of this kind vide ibid., 1907. vol. ii.. p. 255 (Butlin) ; and Lancet, 
1907, vol. ii., p. 1311 (Ryall). 



CHAPTER IX 

CANCER AND TUMOUR GROWTH IN RELATION TO GROWTH 
IN GENERAL 

THE genesis of tumour germs, and their growth, are problems that 
require separate consideration. 

In a previous chapter, comparing tumour germs with ova, I insisted, 
with reference to their origin, that just as cells embedded in the stroma 
of an ovarium become ova by excessive growth at the expense of adjacent 
nutritive materials, which they divert from other cells ; so it may be 
inferred that those cells which originate tumours, become different from 
their congeners' in a similar way. 

It will, I think, aid us in arriving at correct ideas as to the nature and 
conditions of tumour growth, if we extend our analogy, so as to embrace 
also this part of the problem ; that is to say, by comparing tumour growth 
with the growth from the ovum for no doubt all the attributes of tumours 
are but the consequences of their modes of growth. 



Of Growth in General. 

But, before entering on this matter, it seems desirable briefly to survey 
the subject of growth in general. 

At the outset it must be mentioned, that growth is always accompanied 
by marked changes of form ; and, moreover, for each kind of being and 
for each part, growth has a determinate limit. With regard to the 
various parts and organs, their growth in the course of ontogeny is by 
no means uniform ; for, while in some the process ceases, in others it is 
renewed with fresh vigour. Indeed, the ontogeny of every higher organism 
presents a twofold progress, proceeding pari passu. On the one hand, 
there is continuous perfecting of bodily structure by increasing histo- 
logical and morphological differentiation, whence the various tissues and 
organs result ; and, on the other hand, there is continual transition from 
lower and more general, to higher and more specific types of organization. 

The most remarkable of these morphological manifestations of growth 
take place in young animals, especially during the embryonic period ; 
but, changes of this kind also occur in post-natal life, even in mankind 
and the highest animals, of which examples are seen in dentition, puberty, 
pregnancy, lactation etc. 

The earliest products of the histological differentiation of the 
embryonic epiblast and hypoblast, are layers of the epithelial cells which 

201 



202 THE NATURAL HISTORY OF CANCER 

function as the primitive organs. The organs of the adult are evolved from 
these layers by further differentiations : certain of their cells become as 
it were the germs, whence these organs bud forth in a definite and orderly 
manner, the essence of the process being that at certain points more 
intense cell proliferation sets in than elsewhere. Solid bud-like processes of 
proliferous cells thus arise ; which, as they increase, grow into the adjacent 
tissues. The further development of such a bud or initial cellular mass 
may be either continuous or discontinuous : it may spread as ingrowth, 
outgrowth, or sometimes as both, the ultimate form of the resulting 
organ being only gradually attained through subsequent successive 
modifications. 

In these various types of normal epithelial new formations, we see the 
prototypes of corresponding pathological new formations. In all cases, 
these morbid productions seem to result from a modified, super-induced 
repetition of some portion of the normal developmental process of the 
affected part or its vicinity. Just as there are good reasons for believing 
that the primordial starting-point of every organ is a single cell ; so, 
likewise, we may conclude that every tumour probably has a similar 
origin. This need excite no surprise, when we recollect the wonderful 
reproductive properties of cells. 

Under normal conditions, growth proceeds in a regular and orderly 
manner, in accordance with the specific hereditary tendency of the 
whole ; and, just as the great problem of physiology is to explain this 
orderly sequence, so the great problem of tumour pathology is to explain 
how, under abnormal conditions, the disordered rhythm of growth is 
produced of which tumours are the outcome. 



Of Growth in Cells. 

Ever since the establishment of the cell theory, it has become clearer 
and even clearer, that the solution of all biological problems including 
those of tumour formation must ultimately be sought in cell life and 
cell processes. We will therefore proceed with our task by studying 
growth in the individual cell. As the one really essential, universal, 
physiological property common to all living things, growth is a pheno- 
menon of the greatest importance. To our senses cell growth manifests 
itself as a rhythmic process, in which increase of size alternates with 
increase of number or multiplication ; and, at the same time, there is 
concomitant structural differentiation of the growing unit, that is to 
say, change from the general to the special. This change is commonly 
termed " development," and is often held to be fundamentally distinct 
from growth. It may be said that growth is due to the tendency of like 
units to unite, and of unlike units to separate ; or, as Spencer has it : 
" Growth is an integration with the organism of such environing materials, 
as are of like nature with it." All living things grow by taking into their 
substance new particles, which they dissolve and convert into new living 
matter. This latter, the physical basis of life, is the nitrogenous carbon 
compound protoplasm ; of which it may be said, that its molecules are 



CANCER AND TUMOUR GROWTH 203 

of such kinds and so compounded, as easily to admit of rearrangement. 
Thus, its constitution specially fits it to receive and produce the internal 
changes, required to balance the external changes, the continuous adjust- 
ment of which according to Spencer constitutes life. 

The young cell is small ; it increases in size, through the assimilation 
by its elements of a larger quantity of nutritive materials, than is required 
for the repair of waste and maintenance (anabolism). Having thus 
attained a certain normal size, which varies for different kinds of cells, 
this excess of nutritive materials is dissipated and used up for the 
production of new cells (katabolism) ; that is to say, there is reproduc- 
tion, multiplication, or growth of the cell beyond its individual limit of 
size. 

As to the real nature of the force which determines the limit of cell 
growth and its form, we can only surmise that it has some similitude to 
crystal formation. Just as, in the latter, we see that the whole aggregate 
exerts a force, which constrains the newly integrated units to take up a 
certain definite form ; so, it may be assumed, the rearrangements of 
organic units are determined in a somewhat similar way. This hypo- 
thetical property, as to the real nature of which we are in both cases 
ignorant, is called polarity. Thus regarded, polarity may be defined 
as the resultant of the physico-chemical forces which determine mole- 
cular arrangement ; hence, in the evolution of organic form, the polarity 
of protoplasm is a very important factor. 

It is also noteworthy, that the size and qualities of particular cells 
depend chiefly upon heredity, that is to say, upon inherent potentialities 
of parental origin. 

In every act of reproduction, a certain quantity of protoplasm is 
transferred from the producing to the produced cell ; and, along with 
it, the molecular motion peculiar to the parental unit. The phenomena 
of heredity are, in fact, dependent upon this material continuity and 
partial identity, of the producing and produced organisms. 

It is generally believed that each cell, after its formation, begins at 
first to grow slowly, then reaches its greatest rapidity of growth ; and 
ultimately growth declines, until at last it ceases : thus, there is a wave- 
like rhythm, with periods of increase, maturity and decline. According 
to Minot, 1 however, the rate and power of growth steadily decrease, from 
the beginning to the end of life. If we accept this view, it follows that 
stoppage of growth is not due to the attainment of maturity, but is merely 
the final term of a long series of losses ; and, pushing this argument to 
its logical conclusion, Minot maintains that loss of vital force " senes- 
cence " is the stimulus which inaugurates discontinuous growth or 
proliferation. 

In these ways then the form and substance of cells are altered, and 
at the same time their physiological properties are altered, so that new 
relations are established. 

All sorts and conditions of growth in the end, will be found to depend 
upon the molecular processes of nutrition understanding by this term 
the whole of the material changes wrought in the organism, through the 
1 " Reference Handbook of the Medical Sciences," 1889, vol. iii., p. 398. 



204 THE NATURAL HISTORY OF CANCER 

influence of the surrounding outer world. These many complicated 
conditions never being absolutely identical for any two cells, it follows 
that variability is a universal property of all cells. Thus, change of 
nutrition is unquestionably the true cause of all morphological variation ; 
which, according to Virchow, always has its foundation in a pathological 
accident. By disease, in fact, we merely imply a phase of life, whose 
manifestations deviate in some way from the normal, owing to perturba- 
tions caused by changed or abnormal conditions of existence. Thus, 
our conception of disease is a purely physiological conception, which 
recognizes the identity of the laws governing physiological and patho- 
logical processes ; and traces the diversity between the two, to differences 
in the conditions under which the organic forces and substances operate. 
A necessary outcome of this conception of disease is, that every patho- 
logical process has its physiological prototype a great principle of 
modern pathology the full significance of which is, even now, far from 
being adequately recognized. 

In any given case, it is impossible to say where health ends and disease 
begins ; thus, no one can determine where what are called normal morpho- 
logical variations end, and where cancer and tumour formations begin. 
All that we can say is, that when structural or functional changes are 
hurtful, they belong to the province of pathology. The study of healthy 
processes must, therefore, necessarily precede that of the study of the 
phenomena of disease. 

Had the pathologists of half a century ago, been imbued with more 
adequate knowledge and understanding of the fundamental principles 
and methods of biology, our present knowledge of tumour pathogenesis 
would be much in advance of the standard actually attained ; for, even 
now, it is chiefly owing to this kind of defect, that so many modern 
endeavours miscarry. 

Other things being equal, growth varies according to the surplus of 
nutrition over expenditure ; and it is unlimited or has a definite limit, 
according as this surplus does or does not progressingly decrease. 

Why should growth tend in the direction of cell proliferation, rather 
than to the production of large unicellular aggregates ? We must seek 
the answer to this question, in the conditions of molecular cohesion in 
protoplasm. In all cases the process is evidently one of disintegration ; 
and, as such, opposed to that integration which constitutes the individual. 
According to C. F. Wolff, there is a certain relation between the commence- 
ment of the process and declining growth. For cell multiplication does 
not take place while the parental individual is growing rapidly, that is 
to say, while the process of growth greatly exceeds the opposing forces ; 
but it begins, when nutrition is nearly equalled by expenditure. 

It is customary to speak of both protoplasm and nucleus, as the 
essential constituents of a typical cell ; and to these modern cytologists 
add the centrosome. It must, however, be distinctly understood, that 
all the parts of the cell are knit together in organic unity. Most cytolo- 
gists now regard the nucleus as the most important constituent of the 
cell ; and, to this organ, they specially attribute its maintenance and 
multiplication as a living entity. Thus, the nucleus presides over the 



CANCER AND TUMOUR GROWTH 205 

constructive metabolism of the cell, being specially concerned in the 
formative processes involved in all kinds of physiological and patho- 
logical growth and development ; and, it is through the nucleus, that 
specific qualities are transmitted from cell to cell, by heredity. The 
earliest manifestations of all kinds of ceU growth and multiplication are, 
therefore, to be looked for in nuclear changes. Young cells generally 
have relatively large nuclei, surrounded by scanty protoplasm. 

In support of these claims for nuclear pre-eminence, it may be men- 
tioned that Griiber, Nussbaum and others, have shown that when uni- 
cellular organisms are artificially divided, only those fragments which 
comprise nuclear elements, are capable of growing and multiplying the 
others gradually perish. 1 

The centrosome is a minute body, or pair of bodies, which lies in the 
cytoplasm near the nucleus, surrounded by the rounded attraction 
sphere (archoplasm), or by a cytoplasmic radiating aster. It is regarded 
by Boveri and other cytologists as the special organ of proliferation ; 
and, therefore, the dynamic centre of the cell. The precise status of the 
centrosome is, however, still sub judice. 

Growth being an integration with the organism of such environing 
matters as are of like nature with it, is necessarily dependent upon the 
available supply of such materials : of these the most essential is water, 
for it is certain that living things cannot grow without it, however abun- 
dant the other requisites may be. Light, heat, and nutriment are als 
important factors. The quality and quantity of nutritive material at 
the disposal of a cell, has a profound influence upon its behaviour. 

In cell proliferation, to which all organic units are inherently prone, 
the occurrence and nature of the process whether by agamogenesis, 
gamogenesis, or alternation of generations is determined by the con- 
ditions of nutrition. Impregnation may be regarded, as merely one of 
the various conditions, which affect the process : the influence of the male 
element on the germ-cell, as Caspar Friedrich Wolff long ago suggested, 
being comparable to that of a kind of nutriment. 

There are good reasons for believing that, in unicellular forms, life 
runs in cycles of asexual cell divisions, which are strictly limited the 
separate cells of one such cycle being collectively analogous to the entire 
body of a multicellular organism. Each of these cycles begins and ends 
with an act of conjugation. In support of this conclusion, Maupas' 
researches on infusorians may be instanced. By following for a long 
period the life-history of various species, through the entire cycle of their 
existence, he showed that after a time the processes of growth and 
development in these unicellular animals, tended to come to an end, owing 
to 4i senescence "; and this defect could only be overcome by conjugation. 
Thus, having isolated an infusorian, which in the course of several months 
produced agamically 215 generations, Maupas found that the individual 
cells were exhausted ; and, the return to their normal standard of vitality 
could only be effected, after conjugation with an alien strain. In the X 

1 It has, however, recently been demonstrated by Boveri and Delage, that denucleated 
eggs of the sea-urchin can be fertilized, when they give rise to normal gastrulae and larvae ;. 
so that, if these experiments are substantiated, the nucleus is not the sole vehicle of 
heredity. 



206 THE NATURAL HISTORY OF CANCER 

absence of this union, the race died out. Thus conjugation was shown to 
be requisite, for restoring to the cells their exhausted vitality union of 
the nuclei of the conjugating cells being an essential part of the process. 
In this way, the physical admixture of protoplasmic matter from two 
different sources, is ensured. The new cell thus produced must be 
regarded as an entirely new formation, since in it the characters of both 
the conjugating cells are potential. 

Many biologists have proved that abundant nutrition favours asexual 
proliferation : thus Zacharias found that planarians multiplied rapidly 
in this way, when copiously supplied with food ; but, when the latter 
was withheld or greatly reduced, asexual multiplication ceased. In like 
manner Maupas, having restricted infusorians to vegetarian diet, noted 
great diminution in the rate of the asexual cell divisions. 



Growth in Multicellular Organisms. 

Just as the constituent elements of single cells, together with their 
various differentiated parts, e.g., nucleus, centrosome, etc., are knit 
together into an organic unity ; so, in like manner, the constituent cells 
of the multicellular organism, are also integrated and co-ordinated into 
one organic whole, notwithstanding the structural and functional differen- 
tiations of their constituent cells. In such organisms, the tissue cells 
can only be regarded, in a restricted sense, as being independent units ; 
for their autonomy is subservient, in greater or lesser degree, to the 
requirements of the whole aggregate. 

There can, I think, be no doubt that the activities of the local cells 
are largely controlled by the totality of the forces which determine the 
form of the whole organism ; and the best conception as to the nature of 
this force that biologists have yet evolved, appears to me to be the one 
formulated by Spencer, which represents it as being akin to the force 
which determines the integration of crystals. The tissue cells must 
thus be regarded as local centres of a formative power, pervading the 
growing mass of the whole aggregate. If, during the later stages of 
development, some cells acquire a disproportionately high degree of 
physiological independence, this may be regarded as a secondary con- 
sequence of development, by virtue of which these cells become more or 
less emancipated from the general control. 

The researches of Carnoy and other cytologists give some warrant for 
this conception ; for, they have demonstrated that the constituent cells 
of multicellular organisms, are knit together by protoplasmic cell- 
bridges (ponts intercellulaires), in which cell membrane, protoplasm, 
and sometimes even nuclear filaments, are involved (Ide). Hence it 
may be inferred, that besides serving as nutritive channels, these bridges 
also transmit physiological impulses from cell to cell. 

In view of these discoveries, it seems probable that Heitzmann was 
not far from the right track, when he described the metazoan organism 
as a kind of huge protoplasmic syncytium, of which the constituent cells 
are merely nodal points. 



CANCER AND TUMOUR GROWTH 207 

It is generally admitted that the growth of multicellular organisms 
depends chiefly upon the multiplication of cells, and only to a slight 
degree upon the increase in size of individual cells ; hence, it seems clear, 
that the amount of growth is determined by limitation of the process by 
which cells are increased, both as regards number and rate of multipli- 
cation. 

The question of the causative factors of cell growth and multiplica- 
tion, is the most fundamental and important in the whole range of 
biology physiological as well as pathological and, in the proper under- 
standing of this question, the mystery of cancer and tumour formation 
undoubtedly concentres. 

Biologists have long been aware of the fact, that the unfertilized 
ova of many animals are capable of a certain amount of developmental 
exegesis ; although, after a time, the process usually ceases spontaneously, 
and the cells degenerate and are absorbed. 

In certain exceptional cases, however, the ontological exegesis of 
the egg may proceed to its destination without fertilization ; and, whether 
the development is by gamogenesis or by agamogenesis, seems often to 
depend chiefly upon the conditions of nutrition. 

In this connexion the phenomena of parthenogenesis are of much 
interest, as representing a transition from sexual to asexual reproduc- 
tion. Here germ-cells, which often appear to be formed exactly like 
ova, develop into new individuals, without the influence of any fructify- 
ing sperm. It occurs in certain plants and animals, and is probably 
of the nature of a relapse from the sexual method. 

Among our common honey-bees, male individuals arise only from 
unfertilized eggs by parthenogenesis ; while the fertilized eggs originate 
females exclusively, which evolve into fertile forms (queens), or sterile 
forms (workers), according to the nature of their food. Moreover, it 
appears probable, that the very same egg may develop agamically ; 
which, under other circumstances, would have been fertilized. These 
considerations show, that there is no such fundamental distinction 
between gamogenesis and agamogenesis, as is commonly supposed. 

In true parthenogenesis there occurs along with gamogenesis, in a 
true ovarium or homologous organ, a form of agamogenesis exactly like 
gamogenesis, save in the absence of fertilization, as in silkworm moths. 
False parthenogenesis occurs when new individuals arise from buds in 
pseud- ovaria, which are not ova properly so called, as in Aphides. 

This process is intermediate between true parthenogenesis and that 
form of agamogenesis called by Owen metagenesis, in which new indi- 
viduals bud out, not from any specialized organs ; but from unspecialized 
parts of the parent, which are generally external, but may be internal, 
as in distoma. 

Herein we have evidence that the reproductive properties of somatic 
and of germ cells are the same in kind ; and that they differ only in 
degree. 

We now pass to the very remarkable series of events known as the 
alternation of generations. Until comparatively recently, it was believed 
that in every species the successive generations were always alike 



208 THE NATURAL HISTORY OF CANCER 

homogenesis ; but it is now known that this is not always the case 
heterogenesis. 

Many plants and animals produce a generation unlike their parents ; 
these may produce others like themselves, or like their parents, or like 
neither, and so on ; but eventually the original form reappears. Here 
gamogenesis alternates with agamogenesis or parthenogenesis. 

In further illustration of this subject, reference may be made to the 
life-history of the plant lice (Aphides), which has been admirably worked 
out by Owen, Huxley and others. 

The impregnated ova of the Aphis are deposited at the close of summer 
in the axils of the leaves of the plant infested ; retaining their vitality 
throughout the winter, these ova are hatched by the returning warmth 
of the spring : a wingless hexapod larva is the result. In the pseud-ovaria 
of these imperfect females, there bud forth pseud-ova, which rapidly 
develop into similar imperfect females. At this season no winged males 
have appeared. This process of agamic multiplication continues through- 
out the summer. If the external conditions, such as warmth and nutri- 
ment, continue favourable, eight or more successive generations may be 
thus produced. But, when the weather becomes cold and the supply 
of sap fails in the plant, perfect males and females are produced, which 
by gamogenesis reproduce fertilized ova, thus completing the cycle. 

Further experiments have shown that, in such cases, the rapidity of 
the agamogenesis is proportionate to the degree of warmth and nutri- 
tion ; and that, if the temperature and food-supply be artificially main- 
tained, the agamogenesis continues throughout the winter. When the 
favourable conditions have been kept up for several successive years, 
agamogenesis has likewise continued. In short, it seems probable that 
this agamic reproduction may be continued indefinitely, if all the requisite 
conditions be fulfilled. 

Thus, in these creatures, the summer brood, living under favourable 
conditions of nutrition, reproduce agamically imperfect females ; whereas, 
in the autumn, under less favourable conditions of nutrition, perfect males 
and females are produced. That this is due to the external conditions, 
and not to fixed cyclical routine in the life-history of the organism, may 
be inferred from the fact, that in the favourable environment of a green- 
house, the agamic production of imperfect females may continue for 
years. 

This connexion between sexual reproduction and such diminished 
nutrition as makes growth relatively slow, was first fully made known 
by the celebrated biologist Caspar Friedrich Wolff, chiefly from the 
study of the process in plants. Viewed in this light, gamogenesis is seen 
to be nothing but a particular case of cell multiplication ; and impreg- 
nation merely one of the many conditions which affect the process. 

Seeing that the action of the sperm-cell on the germ-cell was the 
cause of its development for before it was deficient in this respect 
and bearing in mind such considerations as the above, Wolff was led to 
regard the former as nutriment in its highest perfection, supplied to the 
germ-cell from without, instead of through the ordinary channels. 

If we ask modern biologists how fertilization causes the ovum to 



CANCER AND TUMOUR GROWTH 



209 



grow and proliferate, they reply that it is due to the action of local 
bio-chemical or zymotic changes, incited by some substance appertaining 
to the spermatozoon, which probably concentres in its centrosome or 
nucleus, and is therefore exceedingly minute as to its quantity. According 
to Boveri, the ripe ovum comprises all the structures and qualities neces- 
sary for growth, except the centrosome, which is supplied by the sperma- 
tozoon originating the process ; Loeb, however, considers that the 
spermatozoon acts as a catalyzer, merely accelerating a process which 
starts of its own accord. 

The result of some very remarkable experiments in the artificial pro- 
duction of ovular exegesis, especially point to the importance of chemical 
stimuli. 

Under normal conditions, the growth of the egg of the annelid 
Chcetopterus, pauses at the first polar mitosis until fertilized by the sper- 
matozoon, when mitosis is resumed, and both polar bodies are formed. 




MC, Cell wall ; pc, cell protoplasm, showing radiating reticulum, enclosing fluid plasma ; 
mn, wall of nucleus ; pn, nuclear substance, showing reticulum and] plasma ; 
bn, contorted bend of nuclein or chromatin. 

Mead has shown that the same effect may be produced, without 
fertilization, by placing the eggs for a few minutes in a weak solution of 
chloride of potassium. 

Hertwig demonstrated that the unfertilized eggs of sea-urchins may 
be incited to mitotic multiplication, by treating them with weak solutions 
of sulphate of strychnine. 

Morgan found that the unfertilized eggs of sea-urchins and other 
echinoderms, placed for an hour or two in sea-water, to which 2 per 
cent, of the chlorides of sodium, potassium, or magnesium had been 
added, would when replaced in normal sea-water enter on active 
segmentation, the entire mitotic system being evolved under the incitation 
of the chemical stimulus. Morgan also repeated and confirmed Hertwig's 
experiments, as to the similar effects caused by sulphate of strychnine. 

14 



210 



THE NATURAL HISTORY OF CANCER 



The climax of these experiments was reached when Loeb, by carefully 
regulating the strength of his solutions of the above-mentioned chlorides 
and other reagents, achieved the full development of the embryo from 
the unfertilized sea-urchin's egg. Loeb also found that short immersion 
of the unfertilized sea-urchin's egg in sea- water, to which a small quantity 
of acid or alkali had been added, would start segmentation. It was 
subsequently shown by Matthews and others, that similar changes could 
be incited by deprivation of oxygen, by heat, mechanical agitation, ether, 
alcohol, chloroform etc. ; in short, it seems as if any means capable of 




- 



FIG. 11. DIAGRAM OF NUCLEAR DIVISION (WEISMANN). 

r* 1 A, Cell with nucleus (n), and centrosomes (cs), preparatory to division. The chromatin 
forms a thickened spiral thread (chr). B, The nuclear membrane has disappeared. 
Delicate threads radiate from the centrosomes and form a nuclear spindle, at the equator 
of which eight chromosomes or nuclear loops (Jd) are arranged, formed by the splitting 
up of the spiral thread of chromatin in A. C, The chromosomes have each become 
longitudinally split into two, and are about to be drawn apart by the spindle threads, the 
daughter loops passing towards the poles of the spindle, as in D. The cell body then 
divides, each of the resultant cells containing a centrosome and eight nuclear loops. 

producing localized liquefaction of the egg protoplasm, may suffice to 
originate mitotic proliferation. 

Since the nucleus is so largely concerned in the formative changes 
which cells undergo, it is here necessary to refer briefly to its leading 
structural features. Under ordinary circumstances, the nucleus usually 
presents as a more or less globular vesicle embedded in the cytoplasm. It 
comprises a very fine protoplasmic reticulum, the meshes of which are 
filled with granular fluid (plasma). In addition to these achromatic 
substances, the nucleus also comprises a distinctive proteid phosphorus- 
containing substance called nuclein, or from its staining readily chro- 
matin. In young cells, this substance often presents as a long irregularly 



CANCER AND TUMOUR GROWTH 211 

contorted filament (Fig. 10) ; but, in mature cells, it is usually condensed 
into one or more spherical or irregularly shaped masses, which constitute 
the nucleoli. It is in this chromatin constituent of the nucleus, that the 
formative properties of the cell seem specially to concentre ; and, as it is 
the only nuclear substance which passes directly from cell to cell during 
proliferation, it is believed to be the material bearer of hereditary ten- 
dencies. In cells about to undergo division, besides other changes, the 
nuclear chromatin experiences a remarkable series of transformations, 
assuming successively the forms of a coil, wreath, star etc., the outcome 
of which is that the chromatic formation is eventually resolved into a 
definite number of rod-shaped chromatin bodies, known as chromosomes, 
which split lengthwise as the cell divides half of each going to the 
nucleus of the daughter cells. The chromosomes themselves are aggre- 
gates of minute chromatin granules (chromomeres). 

Every species of animal has a fixed number of chromosomes, which 
characterizes the division of all its cells ; for mankind the number has not 
yet been certainly determined, but it is generally believed to be sixteen, 
although some cytologists put it as high as thirty-two, one-half of the 
number being derived from each parent. The essence of this process of 
division is, that the chromatic thread, whether continuous or discon- 
tinuous, splits throughout its entire length into two exactly similar 
halves ; which are then transported in opposite directions, to the respective 
poles of the achromatic spindle, whence they enter into the formation of 
the two corresponding daughter nuclei, each of which thus receives its 
half share of the chromatin, the movement being effected and the spindle 
formed under the influence of the centrosomes. 

All somatic cells multiplying by mitosis are thought to divide in this 
manner, the nuclei of the daughter cells having exactly as many chromo- 
somes, as the parent cell. 

In 1883, Van Beneden discovered that the nuclei of conjugating germ- 
cells, contained only one-half of the number of chromosomes charac- 
teristic of the somatic cells ; and subsequently it was proved that this 
" reduction of the chromosomes " was a universal feature in the matura- 
tion of gamogenetic germ-cells. The peculiar feature of the process is, 
that the chromatin is rearranged and redistributed, without the loss of 
any of its essential constituents. It is clear that this reduction is a pre- 
paration of the germ-cells for their subsequent union ; and the means by 
which the number of chromosomes is kept constant for the species. In 
fact, the essence of fertilization consists in the placing in juxtaposition 
of an equal number of the chromosomes of each parent ; so that the 
offspring may contain all the essential constituents of the chromosomes of 
both parents in about equal measure. Weismann believes that this reduc- 
tion is effected by the extrusion of the second polar body, which removes 
with it the one-half of the chromosomes not needed for gamogenesis. 

Recent researches seem, however, to indicate that similar reduction 
may also occur in the chromosomes of somatic cells, under certain con- 
ditions at present but little understood ; hence, it is evident that the 
problem of reduction and its significance, is still far from having been 
adequately solved. 

142 



212 THE NATURAL HISTORY OF CANCER 



Tumour Growth. 

All that we know of tumours indicates, that they grow and are 
nourished like normal parts of the body ; hence, the growth of tumours, 
like normal growth, is influenced and determined directly or indirectly 
chiefly by the conditions of nutrition, as above set forth. 

We have already seen that the germs of histioid tumours are cells of 
somatic origin ; and that the essence of the neoplastic process consists 
in the awakening, in these cells, of more intense power of growth and 
proliferation than is normal. 

Viewed in this light, tumour formation may be regarded as a dis- 
turbance of the rhythm of growth, by the interpolation in the develop- 
mental series of redundant agamic cell generations, owing to altered 
conditions of nutrition. 

Thus the growth of cancers like discontinuous growth in general, 
of which it is but a particular case is the outcome of a disintegrative 
process, being distinctly related to the decline of growth " senescence " 
of the body in general, and especially of the particular local tissues. 
Hence, while the forces of growth, development, and reproduction are in 
greatest activity during the periods of pre-natal life, infancy, child- 
hood, adolescence, and even adult age the tendency to this disease 
is comparatively small. In both sexes, it begins to be of great frequency 
in the post-meridian period. 

Thus the tendency to cancer-growth waxes, as the developmental and 
reproductive activities wane. The antagonism between the forces of 
genesis, growth, development, and expenditure, is the same in pathology 
as in physiology. In this we see illustrated the universal biological law : 
that growth varies according to the surplus of nutrition over expenditure. 
So long as the surplus exists, that is to say, while growth is active and 
nutrition relatively high, simple continuous increase is maintained ; 
but, when growth declines and nutrition is relatively low, that is to say. 
when it is nearly equalled by expenditure, new centres of development 
are apt to arise, and growth tends to become discontinuous. Changes of 
nutrition determine the transition from the one to the other mode of 
increase ; and so favour the growth of cancer and other tumours, as I 
have previously indicated. 

The physiological paradigms of the neoplastic process are to be found 
in gemmation or agamogenesis especially in that form of it called 
metagenesis, in which the new formations bud out, not from special 
organs, but from somatic elements of the parent, whether these are situ- 
ated externally or internally and even in parthenogenesis. In excelsis 
all of these forms of growth tend to be discontinuous, and they are 
essentially of reproductive import ; but it does not necessarily follow that 
such is always their destiny the process may have a more or less abortive 
ending, eventuating for instance in tumour formation. 

When agamic processes of this kind end in the formation of new 
individuals, it may be assumed that this is a result of their germinal cells 
having acquired complete emancipation from the integrative control of 



CANCER AND TUMOUR GROWTH 213 

the parental organism ; and, conversely, when only such abortive pro- 
ducts as tumours are evolved, the emancipation of the germinal cells 
from this control may be assumed to be much less complete. 

The fundamental nature of the setiological connexion between these 
processes and the conditions of nutrition, I have already sufficiently 
indicated. 

In mankind and the higher animals, except in the very earliest stages 
of ontogenetical development as we have already seen no cells (except 
the ova, which are so differentiated that they cannot respond, until they 
have undergone maturation and fertilization) are ever completely eman- 
cipated ; hence in these, instead of new individuals, such abortive 
formations as tumours result. 

From this standpoint, tumour formation may be regarded as a lapse 
from predominant gamogenesis, in the direction of agamogenesis ; for, as 
the individuality of tumours especially indicates, the process is essentially 
of a reproductive or disintegrative nature. 

In like manner, the different qualities manifested by malignant and 
non-malignant tumours may be interpreted, as I have explained in 
Chapter VII. 

I have previously had occasion to refer to the misleading efforts of 
some biologists, to indoctrinate belief in a fundamental specific distinc- 
tion between somatic and germ cells, which the most detailed histological 
analysis of cellular structure fails to support ; and which is contravened 
in the plainest manner, by many of the most fundamental and important 
facts in the whole range of biology, as I have elsewhere indicated. 

With regard to this doctrine, it may truly be said, that it has no real 
foundation in fact : it is, indeed, the outcome of " muddy speculation," 
starting from an essentially faulty conception ; and, as such, it must be 
regarded as being entirely outside the pale of scientific truth. 

As E. B. Wilson, the chief exponent of modern cytological knowledge 
for English-speaking people, has so well said, in the latest edition of his 
useful book i 1 "All the facts at our command indicate, that the tissue 
cell possesses the same morphological organization as the egg-cell, or the 
protozoan ; and the same fundamental physiological properties as well." 

There can, then, be no doubt, as Spencer and Darwin surmised, that 
the fundamental properties of somatic and germ cells are the same in 
kind, and that they differ only in degree. 

In the growth of malignant tumours, as in the growth of normal 
tissues, differentiation and proliferation seem to be inversely related. 
In a certain general way, it may be said of the metabolism of malignant 
tumours, that the habit of growth predominates over the habit of function 
(Adami). In some animals, it has been found that differentiation is 
concomitant with the loss of certain nuclear structures ; and Boveri has 
suggested, that the exceptional regenerative power of some organisms, 
may be due to retention in latent state, by differentiated somatic cells, 
of reproductive properties derived from the fertilized egg. It may be 
inferred from these considerations, that growing tumour germs owe their 
unusual proliferative capacity, to the relative non-involvement of their 
nuclear substance in the specific changes which determine differentiation. 
1 " The Cell in Development," etc., 1904, p. 291. 



214 THE NATURAL HISTORY OF CANCER 



Recapitulation and General Conclusions. 

In concluding this stage of the argument, a brief recapitulation of the 
chief items thereof may be useful. 

Besides such general causative factors of growth as I have had occasion 
to mention, which are chiefly the outcome of intrinsic forces, there are 
also other considerations which affect the process. Thus, for instance, 
with the growth from the ovum, although the stimulus of fertilization is 
generally necessary for its accomplishment ; yet, the process starts 
independently, and is merely accelerated and completed thereby. That 
this stimulus is not always necessary, is shown by the life-history of the 
common bee, whose unfertilized ova grow " spontaneously " into males, 
while the very same ova, when fertilized, grow into females ; of like 
import are the cases of " true " parthenogenesis, wherein cells which 
are indistinguishable from ova grow into new beings, without any such 
external stimulus. In metagenesis, and in other forms of agamogenesis, 
we see unspecialized somatic cells of diverse parts of the body which are 
certainly neither germ-cells nor ova in the usually accepted sense of 
these terms nevertheless, endowed with the power of growing into new 
individuals, without any other stimuli than those provided by the rhythm 
of growth and favourable conditions of nutrition. Then, finally, we see 
growth from the ovum incited, and even urged to its completion, by 
various chemical stimuli and other extrinsic factors. Thus, the evidence 
that the reproductive properties of somatic and germ cells are the same 
in kind, and differ only in degree, is full and complete. 

It is in the light of such considerations, that the problem of the 
growth of histioid tumour germs must be studied. Indeed, it seems 
certain that the conditions, both general and special, which determine 
tumour growth, are similar to those concerned in the regulation of these 
its physiological paradigms. 

Thus, in the pathological as in the physiological process, besides the 
general causative factors of growth, various other conditions seem to 
affect the process. 

With regard to the influence of nutrition, of which I shall have more 
to say in the sequel, I will now only remark ; that tumours grow, because 
the bodies of the affected persons contain an abundance of materials 
suitable for their nutrition, and stimulating to their formative meta- 
bolism. 

Thus, cancerous tumours consist almost exclusively of albuminous or 
proteid substances ; and, it seems not unreasonable to suppose, that their 
growth may be favoured by excess of these substances in the body and 
especially of such of them as serve as nuclear pabulum. When excessive 
quantities of such highly stimulating forms of nutriment are ingested, 
by persons whose metabolism is defective whether by reason of 
senescence or otherwise there may thus be excited, in those parts of 
the body where proliferative processes are still potentially active, such 
excessive and disorderly cellular proliferation as may eventuate in 
cancer. However this may be, I am persuaded that the ascertained 



CANCER AND TUMOUR GROWTH 215 

facts justify the belief, that there is a certain relation between the con- 
ditions of nutrition and the incidence of cancer growth. 

It seems to me quite clear, that the growth of malignant tumours is 
also favoured by the altered metabolism of the body, consequent on 
decline of the reproductive function. The age-incidence of the disease 
accords with this ; and of similar import is the fact, that malignant 
growths in women occur with great and altogether disproportionate fre- 
quency, after removal of the ovaries for various non-malignant affections ; 
after the destruction of their essential elements in the course of disease ; 
and in cases of congenital absence or defect thereof, of which I shall have 
to say more in the sequel. The great frequency of malignant growths 
in castrated cattle of both sexes, to which Sticker x has specially called 
attention points to the same conclusion ; thus, of 200 bovine animals with 
malignant tumours tabulated by him, no less than 100 were castrates ; 
and of 120 horses with malignant tumours, 51 were castrates. 

It has been suggested that other organs, besides the sexual glands, 
may also influence the general metabolism in such a way, as to retard or 
favour the growth of cancer. Although, in this connexion, there is 
absence of any decisive evidence, such as is forthcoming in favour of the 
r61e of the sexual glands ; it seems desirable, in accordance with the plan 
of this work, briefly to review this line of inquiry, especially as it may 
throw some light on the obscure processes of metabolism, with which 
tumour growth is so intimately bound up. 

The growth of the epithelial tissues of the body certainly varies much, 
and is differently conditioned, at different periods of life. In infancy and 
childhood, as compared with the other tissues, the epithelia are com- 
paratively inactive ; and, it seems probable, that the immunity of children 
from malignant epithelial growths, is in some way connected with this 
physiological quiescence. 2 By what means then, in the healthy body, is 
epithelial growth inhibited and kept within due limits ? To this query, 
the chemical physiologist answers : that it is due to certain bio-chemical 
reactions, in which enzymes play a leading part " anti-epithelial " 
substances being thus formed, which circulating throughout the body 
check the growth of epithelial cells. In like manner, the chemical 
pathologist refers the exuberant epithelial growth of cancer, to absence 
or deficiency of these special substances. 

The organs more particularly concerned in influencing these hypo- 
thetical processes are, according to Sajous, the adrenals, the thymus, 
the thyroid, and the anterior part of the pituitary body the adrenal 
influence predominating. Thus Sajous 3 says: "Certain growths, par- 
ticularly the more malignant forms of sarcoma and carcinoma, seem 
closely connected with adrenal insufficiency and its normal consequences. 
We have seen that trypsin, fibrinogen and the oxidizing substance, were 
simultaneously necessary to ensure the destruction of cells in vitro ; 
and, furthermore, that this process required, in addition, the presence of 
alkaline salts. That the destruction of worn-out or degenerated cells, 
is a function of these very elements in the blood, is evident. Insufficiency 

1 Arch. f. klin. Chir., 1902, Bd. Ixv., Heft 3 and 4. 2 Vide Chapter XV. jj 

3 " Internal Secretions," 1903,- vol. i., p. 785, Philadelphia, U.S. 



216 THE NATURAL HISTORY OF CANCER 

of the adrenals therefore, by reducing the relative proportions of these 
four constituents in the blood-stream, must correspondingly inhibit this 
physiological process in all parts of the system." 

In comparatively recent times some remarkable instances have been 
reported, which show that there is some setiological connexion between 
ovarian and adrenal integrity ; and the growth of malignant tumours. 
Thus, as I have specially pointed out, in a publication on " Precocious 
Sexual Development," - 1 this anomaly is fairly often associated with 
malignant ovarian and adrenal tumours. Bullock, Sequeira, Linser, 
Adams 2 and Guthrie 3 have lately reported additional examples of this 
kind, associated with malignant adrenal tumours ; and I have 4 elsewhere 
cited instances of malignant tumours of various parts of the body, con- 
comitant with non-malignant adrenal tumours. 

Here also it may be mentioned that Drs. Beard and Shaw-Mackenzie, 5 
have ascribed cancer growth to perverted metabolism caused by hypo- 
thetical failure of pancreatic secretion, 6 especially of trypsin ; and they 
claim to have cured " Jensen's tumour " in mice which so often under- 
goes spontaneous cure with injections of this substance. 

Whatever element of truth may be concealed in these obscure pro- 
cesses, it appears to me that these therapeutic suggestions go far beyond 
what is warranted by the known facts ; indeed, it is only with regard to 
thyroid medication which seems to exert beneficial influence on some 
hyperplastic cutaneous maladies, and even on certain cancerous growths 
that we can be said to have any facts at all worthy the name, and these 
are far from warranting such sensational inferences as have been drawn. 

If then I have referred to these matters at all, it is because of 
the possible prospective value of this kind of research, rather than for 
anything that has as yet been ascertained. 

We have already seen that the tissue cells may be incited to abnormal 
growth and proliferation by some traumata, by the toxins of certain 
microbes, by various chemical, electrical, thermal, mechanical, and other 
extrinsic agencies ; although none of these seem able, per se, to carry the 
process on to true tumour formation. Thus tumour germs resemble ova, 
in that they generally require to be matured and stimulated in a par- 
ticular way, before their potential proliferative power can become actual. 

From this standpoint, the problem of cancer growth resolves itself 
into a research, to determine the particular way in which the cells of 
tumour germs may be incited to unfold in sufficient measure their 
potential proliferative capacity. 

Although it is probable that in the past, the value of extrinsic factors, 
as formative stimuli, have been underrated ; it, nevertheless, seems 
probable, from the whole course of ontological growth, that, in tumour 
formation, as in normal growth, intrinsic factors usually predominate. 

1 British Gynaecological Journal, May, 1902. 

2 Transactions of the Pathological Society, London, 1905, vol. Ivi., p. 189. 

3 British Medical Journal, September 21, 1907. 

4 Chapter XIII. 

5 Medical Press and Circular, December 20, 1905, p. 661 ; see also Dr. Shaw- 
Mackenzie's " Nature and Treatment of Cancer," 1905. 

5 As will be mentioned later on, cancer of the pancreas is comparatively rarely 
associated with glycosuria. 



CANCER AND TUMOUR GROWTH 217 

If we ask cytologists to explain, How it is that ova sometimes develop 
parthenogenetically ? they reply, that it is due to imperfect matura- 
tion ; for, cells undergoing this kind of growth, extrude only a single polar 
body, and consequently undergo no reduction of the nuclear chromo- 
somes, which is effected by the extrusion of the second polar body, and is 
preparation for fertilization. Pursuing the analysis further, they main- 
tain that, in parthenogenesis, the second polar body is not really absent, 
but only abortive ; and that this kind of growth is the result of the self- 
fertilization of the ovum, by its abortive second polar body. 

There are, however, good reasons for believing, that this interpreta- 
tion of the process is far from being adequate, since the ova of certain 
arthropods have been seen to develop parthenogenetically, although 
like ova which require fertilization they have produced two polar 
bodies, and have undergone reduction of the chromosomes. Never- 
theless, pathological cytologists are now asking, whether conditions 
of this kind may not play a part in the growth of tumour germs ? So 
far as I know, no one has ever observed in the germ-cells of cancer, 
maturation phenomena like those seen in normal or parthenogenetical 
ova ; that is to say, the formation of polar cells unless, indeed, some 
observations by Paterson * may be interpreted in this sense. It has, 
however, long been known, as specially indicated by Hansemann, 2 that 
among the numerous mitotic irregularities of growing cancer cells, a 
deficiency of the chromosomes (" hypochromatic ") is often noticeable ; 
lately, Farmer. Moore and Walker, 3 have described the occurrence of 
reduction of the chromosomes (" hetero typical mitosis ") like that 
normally met with in maturing germ-cells as being a constant and 
special feature of the growth of malignant tumours. 

Considering how little is known as to the occurrence of this reducing 
process in human tissues, cytologists not even being in agreement as to 
the precise number of chromosomes proper to ordinary somatic mitosis, 
this generalization seems rather premature ; and, it accords with this, 
that reduction of the chromosomes in somatic mitosis has already been 
reported in various processes, having nothing to do with cancer ; and it 
has even been found possible to produce it artificially by chemical stimula- 
tion etc., as previously mentioned. 

It is generally stated that among tumours, only the malignant ones 
exhibit this form of nuclear arrangement ; but Bonney 4 has met with it 
in condylomata, and in ovarian papillomata. 

Since then reduction of the chromosomes is not constant in malignant 
tumours, and since it occurs in the absence of malignancy, whatever its 
significance may be, it cannot be regarded as specific of cancer. It is 
even just possible, that reduction may eventually turn out to be merely 
a phase of senescence in certain tissues. 

It was long ago remarked by pathological cytologists, 5 that the 

1 Practitioner, May, 1904. 

2 Arch. f. path. Anat., 1890, Bd. cxix., S. 299 ; also 1891, Bd. cxxiii., Heft 2. 
" Cytological Investigation of Cancer," Liverpool, 1906. 

4 Transactions of the Pathological Society, London, 1905. 

5 Transactions of the Pathological Society, London, 1888, vol. xlix., p. 409 
(Shattock and Ballance). 



218 THE NATURAL HISTORY OF CANCER 

nuclei of growing cancer cells have a tendency to shed their chromatin 
into the cytoplasm, as a sort of preliminary to division ; and to this 
source the detached nuclear fragments, described by Foa 1 as corps 
colorables, were generally ascribed. Paterson 2 has lately reinvestigated 
this subject, and found that during mitosis certain of the nuclei throw 
out processes like pseudo-podia, this being the first stage of budding, 
or the beginning of the migration of the nuclear chromatin from the cell. 
The appearances seemed to indicate, that such extruded chromosomes, 
and the remainders of such reduced nuclei, may unite by mitosis with 
similarly affected nuclei from other adjacent cells, introducing conditions 
having some resemblance to those described in the formation of abortive 
polar bodies, and in the maturation of parthenogenetic eggs. Whether 
this interpretation of the mechanics of cancer growth will eventually 
be substantiated, remains to be seen. 

Pathologists have, of course, long been familiar with the conception 
which ascribes the initiation of malignant growth, to the conjugation of 
the cell of a cancer germ, with some adjacent somatic cell, as described 
by Strcebe, 3 Hansemann, Klebs and others ; but it cannot be said that 
the doctrine thus advanced carried much conviction. Lately, as the 
outcome of such research tendency as we are now pursuing, this matter 
has again cropped up. 

That leucocytes may not unfrequently be found between, and even 
within, the constituent cells of cancerous tumours, has long been well 
known. Lately, Farmer, Moore and Walker, 4 examining quite young 
cancer formations, found that the histological appearances indicated a 
kind of conjugation between the local epithelial cells and included 
leucocytes, with mixing of the chromosomes of the respective nuclei 
during mitosis, but apparently without reduction ; and to this they ascribe 
cancer growth. 

In studying the cytology of cancer pathologists, as a rule, have paid 
but little attention to the centrosome, to which biologists attach such 
great importance, as the directing centre of formative changes. 

In 1893, however, Galeotti andLustig 5 clearly identified the centro- 
somes in cancer cells ; and published descriptions and drawings of them. 
In resting cells, they found a single centrosome in a depression at the 
margin of the nucleus ; but, in cells entering on mitosis, the two centro- 
somes were found one at each apex of the mitotic spindle. 

Borrel 6 next identified certain rounded " endocytes " or " inclusions " 
commonly found in cancer cells, and often described as sporozoa or 
coccidia, as being the cell archoplasm with its contained centrosomes, 
with which he had previously gained familiarity when studying the 
spermatogenesis of guinea-pigs. 

Le Count, 7 as the outcome of a similar study, supported these con- 

Gaz. degli Ospitali, February 2, 1893. 

Op. cit. 

Ziegler's Beitrage z. path. Anat., 1891, Bd. xi., S. 1. 

British Medical Journal, 1905, vol. ii., p. 314 ; and op. cit. 

Ziegler's Beitrage z. path. Anat., 1893, Bd. xiv., S. 225. 
f 6 Ann. de I'Inst. Pasteur, 1901, vol. xv., No. 2. 
7 Journal of Medical Research, vol. vii., p. 383. 



CANCER AND TUMOUR GROWTH 219 

elusions ; while Hansemann also included the archoplasm, as one among 
the many conditions which give rise to " endocytes " in cancer cells. 

Benda, 1 having found intact centrosomes in cancer cells, in which 
" endocytes " were also present, claims that this disproves Borrel's 
interpretation as to their analogy. 

Farmer, Moore and Walker, 2 having lately retraversed the same 
ground, conclude that these " endocytes " represent not the centro- 
somes, which were discernible elsewhere in the cells ; but the cast-off 
archoplasmic vesicle, in which the centrosomes were originally con- 
tained. 

Whatever the real nature of these " inclusions " may be, they are 
evidently not peculiar to cancer, as Greenough 3 and so many others have 
shown. 

Indeed, it is as yet far too early to estimate the precise significance 
attaching to the various recent cytological findings in cancer cells ; but, 
already it can be clearly discerned, that none of them are specific of 
malignancy. 

The most searching morphological investigations, having failed to 
reveal any specific mark of malignancy, pathologists are now seeking 
for some chemical materies morbi. 

Like so many of our modern conceptions, this is an old favourite in 
new dress. Over half a century ago, in the days of J. Miiller 4 and Lebert, 5 
the chemistry of tumours was very thoroughly studied, with the same 
objective in view ; but no specific substance was discovered. The general 
outcome of these researches was, that the greater the malignancy of the 
tumour, the more albuminous substances predominated in its compo- 
sition ; hence Rokitansky 6 proclaimed that diseased (" kakoplastic ") 
albumin, was the cause of all true malignant tumours. 

Modern physiologists have advanced the hypothesis, that the develop- 
ment of particular structures is determined by specific formative sub- 
stances, which incite corresponding kinds of metabolic activity and 
differentiation : the nucleus, they regard as a storehouse of ferments, 
which pass out into the cytoplasm, and there set up specific activities. 

In like manner, some modern pathologists ascribe the initiation of 
cancer growth, to bio-chemical disturbance of the relations normally 
subsisting between cell, nucleus and protoplasm ; in which, as the result 
of catalysis, there is assumed to be some unusual mingling of enzymes. 

According to Blumenthal 7 and Hemmeter, 8 cancer cells differ 
chemically from somatic cells, comprising substances that have hitherto 
not been found in the normal body ; while Petry claims that there is a 
special intra-cellular cancer ferment which has been called " malignin " 
by means of which cancer cells are endowed with their special qualities. 
These conceptions have very little basis in ascertained fact ; they are 

Verhandlungen d. deuts. Gesellach. f. Chir., 1902, No. 31, S. 73. 

Proceedings of the Royal Society, 1905. 

Third Report of the Croft Cancer Commission, Boston, U.S., 1905. 

" Ueber den feineren Ban und die Formen der krankhaften Geschwiilste," 1838. 

"Traite d'Anat. Path.," etc., Paris, 1857. 

" Handb. der allgern. path. Anatomic," Wien, 1846, S. 530. 

Berlin, klin. Woch., 1905, Nos. 12 to 15. 

American Journal of Medical Science, April, 1903. 



220 THE NATURAL HISTORY OF CANCER 

rather the outcome of a priori considerations, and differ but little from 
Rokitansky's " kakoplastic " albumin, and other kindred speculations, 
which have long since been forgotten. 

Thus chemistry, like morphology, has failed to reveal any specific 
cancer substance, from whose presence this malady must result. 

In the light of these long-continued and repeated failures, we shall 
probably not be far wrong in concluding that there are no specific cancer 
substances, other than such as are concerned in determining the specificity 
of the various physiological tissue elements. 

It will be gathered from the foregoing, that far more may be learnt, 
as to the real nature of the cancerous process and the conditions which 
determine it, from study of the general laws of growth and its rhythm, 
and of their relation to the conditions of existence, which comprise 
nutrition ; than from the mere pursuit of details morphological and 
chemical in ultimate analysis, which lead to nothing more stable than 
a chaos of hypothetical " enzymes," or to other equally unreliable meta- 
physical notions such as credulous and unscientific epochs, like the 
present, are particularly apt to engender. 



Growth, Repair, Regeneration, and Tumour Growth. 

It now remains for me to offer some further remarks on that part 
of this important subject, which relates to repair and the regeneration of 
lost parts, as prototypes of tumour formation. 

In the case of crystal formation, it is obvious that the whole aggregate 
exerts a force, which constrains newly integrated units to take a certain 
form ; and thus crystals are enabled to repair injuries. 

It seems probable that the rearrangements of organic units, which 
characterize the processes of repair aJid regeneration in animals, are 
determined in a similar way. 

According to Herbert Spencer, cells capable of growth completely 
uncontrolled and placed in fit conditions, naturally tend to arrange 
themselves into the form of the organism whence they originated ; thus, 
a small detached bit of a Hydra, soon moulds itself into the shape of an 
entire Hydra. 

On the other hand : " Cells which form a small group involved in a 
larger group, are subject to all the forces of the larger group, will become 
subordinate in their structural arrangements to the larger group, will be 
co-ordinated into a part of the major whole, instead of co-ordinating 
themselves into a minor whole "; hence, the cellular mass which buds 
out in place of a lobster's lost claw gradually assumes the form of a claw, 
that is to say, it has its parts so moulded as to complete the structure of 
the organism. 

It is thus evident that the organism, as a whole, exercises such con- 
trolling power over the newly forming part, as to make it a reproduction 
of its predecessor. 

Structurally regarded, the new formation of repair closely resembles 
that of similarly situated tumours ; and between the reparative and neo- 



CANCER AND TUMOUR GROWTH 221 

plastic processes there is obviously an affinity such differences as exist 
being in degree rather than in kind. Indeed, the grand difference lies 
in this : that whereas the new growth of repair is definitely limited and 
merely suffices to replace what has been lost, the pathological new growth 
knows no such bounds. In the latter case, the normal subordination of 
the local process to the specific hereditary tendency of the whole, has 
been diminished or has ceased to exist. Such a local abnormality of 
growth may then acquire a fixed character, becoming incapable of 
further change except within the limits imposed by its acquired char- 
acter and thus a tumour is formed. 

It has now been clearly established by the criterion of mitosis, that 
the new formation of repair is produced by the active growth and pro- 
liferation of the tissue elements of the affected part, in which leucocytes 
and other cellular elements ab extra are not essentially concerned. 

It has also been ascertained that the rapidity of proliferation in patho- 
logical regeneration, is greatly in excess of that by which the normal wear 
and tear is made good. 

By the same method it has likewise been determined, that reparative 
processes are most prone to arise and are most efficient, in those tissues 
where cells capable of growth and proliferation most abound. 

It has also been proved that the reparative process, like tumour 
formation and the growth ab ovo of which latter it is but a modified 
superinduced repetition in partibus is independent of nervous (trophic) 
and vascular influences (inflammation etc.). 

As in the course of normal development, cell derivatives of the different 
blastodermic layers are never transformed into each other ; so, in the 
reparative new formation, no such metamorphosis ever occurs. Hence, 
no structures of new and specific type are to be found in the new forma- 
tion of repair ; whose elementary constituents, as a rule, resemble those 
of the physiological tissues both genetically and histologically. 

Such at least appears to be the state of affairs in the highest organisms ; 
but, in the lower kinds, as in the Hydra, no such distinction is apparent. 

It seems probable that the tissues of all organisms are constantly 
being destroyed, in the normal exercise of their functions ; and that a 
certain capacity for such physiological repair as is necessary for making 
good these losses, is inherent in all organisms. 

Thus, at certain periods of. the year, many animals by a spontaneous 
and natural process lose certain parts of their body, which are subse- 
quently renewed, e.g., the fall of the stag's horn, the moulting of birds, 
the shedding of the cuticle of serpents and the shell of Crustacea ; while 
holothurians, regenerate the digestive tube, after its voluntary expul- 
sion etc. 

Similarly, under pathological conditions, wounds heal, fractured bones 
are repaired, and lost parts may be regenerated. 

This property is possessed by mankind and the higher animals in but 
a very limited degree ; but its perfection in some of the lower animals is 
truly astonishing. 

Moreover, reparative processes are proportionally much greater in 
the young than in the old of all species, being greatest of all in the 



222 THE NATURAL HISTORY OF CANCER 

early embryo ; and their efficacy gradually diminishes with advancing 
life. 

Hence the larvae of amphibians, which present many parts that in 
other animals are developed only in the embryo state, have also greater 
powers of regeneration than the perfect animals ; and in the larvae of 
insects lost parts are often reproduced, which in the perfect insects 
cannot thus be replaced. 

The various parts and organs of animals are also diversely endowed 
in respect to this faculty, e.g., lizards regenerate the tail, but not the 
limbs etc. 

The general law to which these processes conform, is identical with 
that which holds for reproduction in general ; that is to say, it is greatest 
where organization is lowest, and it almost disappears where organization 
is highest. 

It also appears as if the capacity for repair were inversely related, 
to the amount of energy consumed in the growth and development of the 
individual, and in maintenance of the same. 

Thus, when an animal so low in the organic scale as the Stentor, is 
divided transversely into two or three parts, each of these grows into a 
complete Stentor ; and this, even when the slices removed are only 
half a millimetre thick. It appears, therefore, as if each of the units 
of which a Stentor is composed, is capable of regenerating the whole 
organism. 

Even among animals much higher in the organic scale, such as the 
polypes, similar phenomena are met with. Thus, the experiments of 
Trembley with Hydra show, that when this creature is divided longi- 
tudinally or transversely, or when small portions are merely cut out of its 
body, in all such cases the separated fragments grow into perfect polypes. 
Even when the creature was cut up into as many small pieces as possible, 
-each of these became a pprfect Hydra ; by methods of this kind, from a 
single polyp Trembley produced fifty, each of which grew into a perfect 
individual. 

In this connexion the question naturally arises, as to how small a 
portion of a metazoon organism may contain the force necessary for the 
reproduction of the entire individual ? In the case of Hydra, it appears 
as if almost any minute group of cells, severed from the perfect organism, 
sufficed for this purpose. 

In other lowly organized beings, the power of reproducing new 
individuals is not merely manifested by separated portions of almost 
any part of the organism ; but, in some cases, subdivision even to the 
ultimate morphological units, does not destroy this power isolated 
structural units are, in fact, adequate for this purpose. 

In like manner, as recent experimental researches have shown, 
each of the cells (blastomeres) into which in the higher organisms the 
fertilized germ divides, also retains all the properties requisite for pro- 
ducing the entire organism ; and this is so even up to the eight- or sixteen- 
cell stage (Wilson, Driesch, Zoja etc.). Moreover, pieces excised from 
globular blastulae before invagination, have grown into perfect larvae ; 
.and Roux found that half embryos, evolving from detached blastomeres 



CANCER AND TUMOUR GROWTH 223 

of the frog's egg, finally regenerated more or less completely the missing 
half. 

It appears to me that facts of this kind, which can easily be multiplied, 
contradict Weismann's theory, as to there being specific distinction 
between somatic and germ cells. 

Among other experiments on Hydra, Trembley divided polypes 
longitudinally, when, in less than an hour, each half had rolled itself and 
united the cut edges, so as to constitute each a fresh polyp ; he likewise 
divided them transversely, and having brought the divided halves 
together, found that before the close of the day they had firmly united. 

In like manner, he even succeeded in causing the anterior and posterior 
halves of two different polypes to unite ; and the resultant polyp then 
budded and produced young polypes, both above and below the line of 
union. 

Longitudinal narrow bands cut out of the body of Hydra, too slender 
for their borders to unite to form a tube, nevertheless regenerated com- 
plete polypes, the digestive canal being formed by the development of 
a new cavity in the substance of the separated fragment. 

Here I must mention a remarkable fact : several experimenters have 
found that completely everted polypes still continue to flourish ecto- 
dermal cells quickly taking on endodermal functions, notwithstanding 
their obvious morphological differentiations. 

Imperfect division produced polypes with two or more heads : 
Trembley slit one into seven pieces, leaving them connected by the root, 
and the Hydra became seven-headed ; he cut off the seven heads, and 
they soon sprang up again. By laying open a polyp longitudinally, and 
then notching it in different directions, he produced a compound, arbor- 
escent, plant-like animal with many heads and tails. 

It was specially noticed that these experimentally-produced polypes 
grew much larger, and were far more prolific, .than those that had never 
been cut ; but, the supervention, of gemmation, markedly retarded the 
regeneration after injury. Warmth favoured, and cold retarded it. 

In such cases as the foregoing, the processes of regeneration and repro- 
duction by gemmation are seen to be identical. 

Tubularians and many other hydroids, can regenerate the " head " 
(i.e., hypostome, mouth and tentacles), after decapitation. 

Planarians also possess regenerative capacity in a high degree. 
Duges saw from eight to ten new individuals formed, from sections of a 
single animal ; and it has been observed, that these creatures sometimes 
reproduce themselves spontaneously, in a similar way. When the head 
is damaged they regenerate a new one. 

In the higher actinozoa, half an individual will grow into a complete 
new being ; and star-fishes, such as Nais, may be cut into thirty or forty 
pieces, each of which will regenerate a new individual. 

In the common earth-worm, if the anterior segments as far back as the 
fifth are cut off, the rest of the body will regenerate the lost parts, which 
comprise cephalic nerve centre, mouth, stomach etc. ; and this kind of 
regeneration has been known to occur, as many as five times in suc- 
cession. 



224 THE NATURAL HISTORY OF CANCER 

Two pieces of different earth-worms that have been transversely 
severed, when brought into apposition, may grow together, and so form 
a new worm (Landois). 

When, however, worms are longitudinally divided, each half dies. 

Snails can regenerate parts of the head, including tentacles and eyes, 
provided that the cerebral ganglion is not injured. 

In insecta, arachnida and Crustacea, entire organs such as extremities, 
maxillae, antennae, eyes etc., may "of ten be reformed after loss, provided 
that their matrix survives. 

In crustaceans the power of regenerating lost limbs is highly developed ; 
thus, if the entire leg except the minute pair of proximal segments is 
broken off, a new leg develops from the short stump at the next casting 
of the shell. In like manner, if the eye of a crab is excised, without 
injuring the optic ganglion, a normal eye is regenerated. 

As we ascend in the scale of organization this power, though 
diminished, is still considerable. 

Among the vertebrata, in the case of fishes, regenerative capacity is 
generally believed to be comparatively deficient ; but, it is known that 
fishes can reproduce lost fins especially the caudal fin. 

Far greater reparative powers are possessed by amphibians. In 
many of these the regeneration of an entire limb or a tail, occurs readily ; 
and this even several times over, although with decreasing completeness. 
Spallanzani cut off the legs and tail of a salamander six times, and 
Bonnett eight times, successively ; and they were reproduced. In these 
animals the lower jaw, when damaged, is also reformed, provided the 
stump is left. As the observations of Gotte, Fraisse, and Wendelstadt 
show, when the fore-limb of a newt (Triton) is amputated between the 
shoulder and elbow, not only is the lost portion of the humerus formed 
afresh ; but the radius, ulna, and all the bones of the wrist and hand, are 
regenerated accurately, even as regards the number of segments. It 
seems hardly credible that such a complex of structures could be repro- 
duced, merely by the co-operation of the local proliferating cells, without 
the agency of some integrative force to direct the process in accordance 
with the specific hereditary tendency of the whole. 

In these regenerative processes, the developmental changes are 
modelled after those of the normal ontogeny ; and, in the one, as in the 
other case, each specific tissue element only reproduces its own kind of 
cells. Hence, the regenerative process always proceeds from the injured 
part remains of the severed periosteum, endosteum etc., being essential 
for the process ; so that, when the limb is disarticulated at the shoulder 
girdle and the bones are uninjured, the latter are not reproduced. 

In the Triton, Blumenbach has seen the eye, with cornea, iris and lens, 
regenerated within the space of a year ; in comparatively recent times, 
Wolff, Mueller and others, having removed the lens of the eye of larval 
salamanders, found that it was perfectly regenerated. 

The skin of amphibians is readily regenerated after considerable areas 
of it have been destroyed ; and this reproduction comprises not only the 
whole epidermis, but also the various glands and tegumentary sense 
organs (Fraisse). 



CANCER AND TUMOUR GROWTH 225 

Only the larvae of the tailless batrachians (frogs etc.), and not the 
adults, are capable of reproducing lost members ; but regeneration is so 
complete in frog tadpoles, that when the tail is cut off, it is reproduced, 
together with the notochord. 

The tail of a lizard is soon restored after it has been cut off ; but, as 
compared with the original tail, the new one is structurally defective in 
several respects. Thus, instead of the segmented vertebral axis, it often 
happens that only an unseg'mented cartilaginous tube is formed, with no 
trace of notochord ; and, instead of the spinal cord, only an epithelial 
tube is reproduced, which gives off no nerves : moreover, the scales of 
the regenerated tail are often markedly different from those of the 
original one. Lizards are unable to regenerate lost limbs ; as also are 
chelonians, and crocodiles. 

In such instances of regeneration as the foregoing, the newly formed 
part is always very like its prototype ; but, I must now mention that 
the lost part is fairly often replaced by a structure different from the 
original (heteromorphosis). These heteromorphic growths are of special 
interest, as constituting a connecting-link between the new formations 
of repair, and tumours. 

I have already called attention to the fact that, in pathological re- 
generation, the rapidity of the growth greatly exceeds the rate of the 
corresponding physiological process ; and it was also mentioned, that 
polypes produced from dissevered fragments of Hydra grow much larger, 
and are far more prolific, than those which have never been cut. In 
accordance with these indications, we find that redundancy is the pre- 
dominant feature of these heteromorphic manifestations. Thus, the 
regenerated rays of star-fish are often bifurcated, or present supernu- 
merary parts. 

Loeb found that when a tubularian stem is cut off at both ends and 
inserted in sand, with the oral end buried, a new head is then regenerated 
from the free end, which was formerly the aboral end. When such a 
piece was suspended in water by its middle, a new head then formed at 
each end ; while when both ends were buried, neither regenerated. This 
shows that the regenerative process may be modified by external con- 
ditions. 

On excising the stomach and ventral nerve-cord of the earth-worm f 
after having removed the ventral halves of the fourth, fifth and sixth 
segments, Weldon noted that a new head grew out of the gap, producing 
an extraordinary double-headed monster. 

Duges found that planarians, notched in the oral region, regenerated 
with two heads ; and, when similarly treated at the opposite end, two 
tails resulted. 

In a crayfish, whose nipping claw had been irregularly amputated, 
Maggi saw a double claw form in its place ; and in other crustaceans 
similar happenings have been noted. 

Among amphibians, many instances of this kind of anomaly have 
been met with : in the axolotl of his aquarium, Vulpian saw a bitten-off 
extremity regenerated, and at the same time a redundant digit formed ; 
in certain tritons the same occurrence has been noted ; while Piana 

15 



226 THE NATURAL HISTORY OF CANCER 

caused polydactylism in these creatures, by notching the carpus or tarsus 
with scissors. 

In frogs, which as a rule do not regenerate lost limbs, redundant limb- 
like structures have several times been seen to spring from the stump of 
an extremity removed by operation. 

By cutting off the tail of salamanders, lizards etc., and notching 
the stump, Loeb and others saw double and even multiple tails form. 

It has also been remarked that when the amputated tail of a lizard is 
reproduced, the scales of the regenerated part are unlike those of the 
original organ, resembling, indeed, those seen only in certain ancestral 
forms. This experience recalls the somewhat similar heterotopia met 
with in certain galls, as previously mentioned. 1 

The experiments of embryologists, at very early developmental periods 
have yielded results of similar import to the foregoing : thus, by ligatur- 
ing the nascent medullary plate of an evolving triton germ. Spemann 
saw a new head form, from the anterior end of the posterior part of this 
medullary plate, which was just as perfect as if it had evolved from the 
anterior part of the undamaged plate, as in the normal course of ontogeny. 
It is thus evident, that all the complicated structures concerned in the 
head, can be evolved from parts, which if development had proceeded 
normally would not have participated in the formation of head struc- 
tures. It may be inferred from these experiments, that each blastomere 
or group of blastomeres of the evolving germ has the power, when 
isolated, of forming a new individual. 

It seems to me that the neoplastic process is a phenomenon of the 
same order, as these heteromorphic new formations of regeneration. In 
both cases the essence of the process is that, at certain points, more 
intense cell growth and proliferation sets in than elsewhere. The differ- 
ence between them, is merely one of degree the emancipation of the 
proliferating cells from the control of the whole organism, being greater 
in the latter than in the former case. The precise nature of the resulting 
structure seems to be determined by the particular relations which each 
part has with the environment, either habitually in the individual or 
occasionally in the race. 

It accords with this, as I have previously indicated, 2 that, in the 
higher animals and in mankind, many instances are known in which 
malignant and other tumours have developed directly from the new 
formation of repair. 

In the highest animals and in mankind, lost parts are never regene- 
rated : in these, it is only single tissues and their derivatives that are 
reproduced ; but, their wounds heal readily, broken bones are repaired, 
and in other ways reparative processes are active. 

It is, however, alleged that supernumerary digits have been partially 
reformed after amputation, even in human beings ; and the occasional 
hetero-morphic formation of imperfect nails on the stumps of normal 
fingers after amputation, seems to be an outcome of the same tendency 
in a slight degree. 

According to J. Y. Simpson, in early embryonic life, some power of 

1 Chapter VI. 2 Chapters V. and XI. 



CANCER AXD TUMOUR GROWTH 227 

reproducing lost parts may be met with even in mankind ; and he claims 
to have demonstrated several instances of the reproduction of rudi- 
mentary digits, after the amputation of limbs in utero by bands, etc. 

Of like import is the recurrence of subungual exostosis of the great 
toe, when the matrix of the new formation is not thoroughly extirpated ; 
for, as I have elsewhere shown, 1 this new formation is in its nature akin 
to digital redundancy at its minimum. 



The Reparative Capacity of the Human Tissues. 

In human tissues, the reparative process conforms to the same laws 
as those which apply to regeneration in general ; thus, this capacity is 
least in the highly specialized tissues (e.g., muscle and nerve), and greatest 
in the comparatively undifferentiated (e.g., the epithelial and connective. 

Since the discovery of " mitosis " as a criterion of the proliferative 
activity of the cells, it has .become possible to determine accurately both 
the intensity and the duration of tissue repair, and to trace its histogenesis. 
By this method it has been proved, that the new formation of repair 
is the product of the proliferation of pre-existing tissue cells ; and not of 
leucocytes from the adjacent bloodvessels, as was formerly believed. 

Studies of this kind have shown, that in some tissues the constituent 
cells continue to multiply throughout the life of the individual (dementi 
labili) ; or, at any rate, up to some time after birth (elementi stabili) ; 
and these, as Bizzozero has indicated, repair their losses with great 
completeness. Such tissues comprise the epithelial whether disposed 
as a covering or in glandular arrangement connective tissue in general, 
unstriped muscle, bloodvessels, periosteum, bone etc. These are the 
tissues of which the matrix of histioid tumours are composed. 

In another group of tissues, multiplication of the cells by mitosis 
ceases in early embryonic life, before their elements have assumed 
specific character (elementi perenni) ; these (which comprise the striped 
muscles and nerve tissues) never regenerate completely, and hardly ever 
originate malignant tumours. 

The process of tissue repair is modelled after the same plan as the 
process of tissue development in ontogeny, of which it is but a modified 
superinduced repetition : in both cases, proliferation of the tissue elements, 
and not inflammation, is the real starting-point, while bloodvessels and 
nerves are at first absent. 

In all these respects, the analogy between the reparative new for- 
mation and tumour growth is very striking ; and, as we have already 
seen, tumours sometimes arise directly from these reparative new 
formations. 

It has lately been shown by Loeb, 2 Fischer, 3 and others, that all the 
essential histological features of malignancy are reproduced in the 
behaviour of the epidermis, during the heading of wounds. Thus, the 
epithelium on each side of superficial cutaneous wounds was found to 

1 Bristol Medico-Chirurgical Journal, March, 1904. 

2 Johns Hopkins Hospital Bulletin, January, 1898. 

3 Munch, med. Woch., 1906, Bd. liii., S. 2042. 

152 



228 THE NATURAL HISTORY OF CANCER 

fuse into syncytial masses, whence branching processes budded out, not 
only bridging the gap, but also growing downwards, into and through 
the subjacent clot, penetrating the underlying damaged tissues and even 
cartilage, just as happens in cancer. Indeed, it is suggested that this 
penetrative quality of the ingrowing cells is due in the one as in the 
other case to enzyme action. However this may be, it is now evident 
that there is not only anatomical, but also physiological resemblance, in 
the two processes. 



CHAPTER X 
THE MICROBIC THEORY OF CANCER 

ALTHOUGH it appears to me, for reasons set forth in previous chapters, 
that the influence of extrinsic factors is no more necessary to account for 
the origin and growth of a tumour, than it is to account for the origin and 
growth of a tooth or a hair ; yet, I think it is a mistake to deny on 
a priori grounds, the possibility of irritants db extra inciting tumour 
germs to such proliferative activity, as may eventuate in tumour 
growth. 

No one has, indeed, ever succeeded in intentionally producing any 
kind of tumour by such extrinsic agencies ; although, by means of this 
kind, as we have already seen, somatic cells may be incited to prolifera- 
tion, which sometimes results in the formation of tumour-like pseudo- 
plasms of malignant aspect, of which I shall have more to say in the 
sequel. Among such extrinsic agents, microbes and their toxins hold an 
important place. 

I cannot, therefore, concur with Ziegler, 1 when he says : " All the 
biological characters of tumours testify against their parasitic origin." 
My objection to the doctrine of extrinsic tumour pathogenesis is rather 
based upon the fact, that the balance of available evidence, on con- 
sideration of the ensemble of the subject, seems to be decidedly against 
it. Moreover, as the phenomena of the disease can be so much better 
explained without invoking the aid of this hypothesis, as a primary 
setiological factor, it seems to me that we ought to leave it aside, until 
much stronger evidence in its favour is forthcoming than any at present 
available. The need for so doing becomes all the more obvious when we 
recollect, as in the course of my narrative I shall proceed to show, that of 
the many pathologists who claim to have discovered the cancer parasite, 
all are in disaccord as to its nature ; thus, it has been ascribed to bacteria 
of many different kinds, to various protozoan parasites, to diverse kinds 
of fungi, and various other lowly parasites and pseudo-parasites. The 
truth is, most pathologists are so strongly prepossessed in favour of the 
conception that nearly all diseases, not obviously due to some gross 
external cause, must be of parasitic origin, that it is difficult to get them 
to regard this malady from any other standpoint. Hence, although the 
microbe of cancer has not yet been discovered, the microbic theory is 
still the order of the day. 

Of course, the mere fact that no specific cancer microbe has yet been 
discovered, does not per se prove its non-existence for, of many maladies 

1 Munch, med. Woch., 1898, Bd. xlv., S. 312. 
229 



230 THE NATURAL HISTORY OF CANCER 

almost certainly parasitic (e.g., small-pox, vaccinia, measles, scarlet fever, 
syphilis etc.), the same may be said ; and, as is within the recollection of 
every one, the microbe of tubercle was only discovered in 1882. 

Neither can the absence of contagion per se be regarded as proof of 
the non-existence of a cancer microbe ; for some maladies, although 
demonstrably of parasitic origin, are not transmissible by ordinary con- 
tagion (e.g., malaria, coccidial disease of rabbits etc.). 

One of the most remarkable properties of malignant tumours, is their 
power of continuous autonomous growth and development (individuality), 
upon which their so-called parasitism depends. It is by virtue of this 
property that they persist, and tend to increase indefinitely. Inflam- 
matory pseudo-plasms, on the other hand, after a time tend to disappear ; 
nevertheless, there are exceptions, for some pseudo-plasms, such as 
mycosis fungoides, as well as certain tuberculous, actinomycetic, syphi- 
litic and some other pseudo-plasms, are often very persistent. 

A striking feature about cancerous growths, is the great morphological 
difference that obtains between them, according to the localities whence 
they originate. What, for instance, can be more divergent in this respect, 
than the appearances presented on microscopical examination, by sections 
of cancer from such different parts as the breast, the stomach, and the 
skin ? We learn from such examinations, that cancerous growths are 
sufficiently organized, to present unmistakable histological resemblance 
to the structures whence they originate. Herein they differ from most 
inflammatory pseudo-plasms, which present the same granulomatous 
structure, no matter in what part of the body they arise. When, how- 
ever, epithelial elements are included in proliferating granulomatous 
tissue, they are often thereby incited to grow and proliferate, of which 
" Jensen's tumour " is an example in mice ; and, in humanity among 
many such instances uterine " erosions " may be cited. 

The great resemblance always noticeable between primary and 
secondary cancerous growths is a phenomenon of similar import, which 
cannot be accounted for on the basis of inflammation and micro-organisms. 
It is impossible to conceive a valid explanation of such conditions, 
without the presence of cells capable of reproducing their like by 
growth, multiplication, and organization. I am aware that microbists 
make light of this objection, alleging that the emigrant cancer cells 
carry their parasites with them to their new habitat, where the 
said parasites cause a repetition of the initial morbid process. But, 
independently of the fact that cells invaded by parasites tend to 
lose their power of growth and proliferation, it never seems to have 
occurred to the authors of this suggestion, how unlikely it would be for 
microbes transported, for instance, into the liver, to produce in this 
organ the typical structure of breast cancer. Surely, if the secondary 
lesions were really due to microbes, these might be expected to incite 
the liver cells to malignant growth ; and so to cause the formation of 
typical hepatic cancer. As Moxon has sagely remarked : " The first 
cancer which appears has a likeness to the part in which it appears, and 
the secondary cancers arising from it have the likeness of that first 
cancer ; and, those that doubt that they came from that first, cancer, 



THE MICROBIC THEORY OF CANCER 231 

must show us why they have that likeness." In this connexion, Waring's x 
experiments are of interest, for they show that the cellular elements of 
the secondary, as well as those of the primary growths, in cancer of the 
pancreas and stomach, produce the same ferments etc., as the normal 
secretory cells of these parts. 

Thus may be explained the great resemblance always noticeable 
between the primary and secondary growths, the significance of which 
it is impossible to ignore. In short, these phenomena clearly imply that 
the disease centres in the tumour cells themselves ; and not in any 
extraneous condition. Thus, this peculiarity of malignant tumours, 
marks them off from microbic pseudo-plasms, more definitely than any 
other single item. 

In like manner, the peculiar age and sex incidence of the malady, and 
the occurrence of congenital cases, testify against its parasitic origin. 

Such then are some of the reasons for regarding the microbic theory of 
cancer as improbable. 

Before a disease can properly be called parasitic, the parasite must 
be found, isolated ; and, the disease it is alleged to cause, must be repro- 
duced by its inoculation. Judged by this standard, the microbe of 
cancer has not yet been discovered ; for, none of the bodies hitherto 
described as such, comply with these requirements. Of the numerous 
researches undertaken during the last quarter of acentury with a view to 
finding it, all have proved abortive. Where now are the specific cancer 
microbes of Rappin, Freire, Scheuerlen, Schill, Francke, Lampiazi- 
Rubino, Sanarelli, Kiibasoff and Doyen ; of Pfeiffer, Thoma, Wickham, 
Sjobring, Soudakewitch, Ruffer, Walker, Plimmer, Adamkiewicz, 
Korotneff, Juergens, Bosc, Leyden and Schaudinn, Schuller, Gaylord, 
Feinberg, Robertson and Wade ; of Russell, Sanfelice, Niessen, Bra, 
Monsarrat, Leopold, 0. Schmidt etc. ? One after another, the alleged 
discoveries of this recalcitrant organism, have ended only in disappoint- 
ment. The negative results of numerous implantation and other similar 
experiments, as previously detailed, point to the same conclusion. 

In short, the evidence hitherto adduced as to the existence of a specific 
cancer microbe, is altogether inconclusive ; hence, if there really is any 
microbe, from whose presence in the body cancer must necessarily 
result, I can only conclude that it altogether transcends present ex- 
perience. 

As soon as the microscope had revealed to pathologists the wonders 
of the infinitely minute, the medical world expected that some definite 
morphological element would soon be found distinctive of cancer. The 
search for specific cancer elements, although discouraged by J. Miiller 
and Virchow, was keenly pursued by others ; and Lebert soon announced 
that he had discovered the specific cancer cell. When this claim proved 
untenable, the turn of the nucleus came and its mode of division (mitosis) ; 
while lately, as we have already seen, the centrosome has been similarly 
regarded. The minutest cytological investigations having, however, 
failed to reveal the long-expected specific element of cancer ; and, chemical 
researches in this direction having proved equally futile, it remained for 
1 Journal of Anatomy, October, 1893, p. 142. 



232 THE NATURAL HISTORY OP CANCER 

the microbists to complete the search. It is to this popular demand for 
a materies morbi, to this desire for some tangible and concrete if empirical 
explanation of the phenomena of malignancy, that the microbic theory 
of cancer really owes its vogue. Limited to non-malignant tumours, it 
would probably have gained but few adherents ; hence the battle as to 
its relevancy, has centred round the pathogenesis of malignant tumours. 

These the microbic theory regards as the product of " chronic inflam- 
mation," consequent on " irritation," resulting from the presence in the 
tissues, or in the cells, of living organisms or their toxins. It attributes 
not only the initiation of the abnormal growth, to parasitic activity ; 
but also its progress and continuance. Thus regarded, malignant tumours 
would be classed with the infective granulomata. 

Thus the conception of the microbists as to cancer genesis, is an 
exact reproduction of the doctrine of Broussais, so extensively held at the 
beginning of the last century, plus microbes. 

It is presumed that the special action of the parasites in causing 
malignancy, is mainly due to the fact that they often penetrate into the 
constituent cells of the tumour and dwell there, as it were in symbiosis 
the union being so intimate that as the parasite proliferates, so also does 
the nucleus of its epithelial host. It is, however, a remarkable fact - 
which none of those who have investigated the subject have yet explained 
that the nucleus ofc a cancer cell invaded by " parasites," always 
appears to be in a state of degenerative, rather than of proliferative, 
activity. It accords with this, that these " parasite-containing " cells 
are very inapt at proliferation, or do not proliferate at all. 

As to the life-history of this hypothetical parasite, nothing is yet 
known ; but, on a priori grounds, it is presumed to have some analogy 
with that of the tubercle bacillus etc., beginning with a primary lesion at 
the site of inoculation, and being followed by generalization. Metchnikoff , 
however, maintains that it should be classed with the miasmatic diseases, 
and that like malaria it is probably propagated by spores formed 
outside the body, the incubation period varying from a few days to a 
few years. 

In order to test the validity of such statements, investigators have 
for some time been very busy in endeavouring to discriminate and 
isolate these supposed parasites ; to get pure cultures of them ; and by 
inoculation to reproduce the disease in animals, afterwards recovering 
the " parasites " from the latter. Such is the aim of all recent researches 
on this question. 

It is necessary to insist on the rigid enforcement of these precautions 
before arriving at any definite conclusions ; for only thus can we avoid 
being deceived, by what Pasteur calls the besetting weakness of medical in- 
vestigators, viz., their unfortunate tendency to generalize by anticipation. 

As Crookshank says : " It is of very little value merely to detect or 
artificially to cultivate a microbe associated with disease. We must 
endeavour to establish its exact relationship with the morbid process ; 
and the determination of the true pathogenic value of a microbe is beset 
with many fallacies." In the sequel, the necessity for regarding this 
word of caution will be abundantly manifest. 



THE MICROBIC THEORY OF CANCER 233 

It is a well-recognized rule in pathology although more honoured 
in the breach than in the observance that familiarity with the minute 
anatomy of a part and of its various morbid variations, should precede 
the special study of any supposed pathological novelty. 

It must be confessed that the original investigators of the so-called 
parasites of cancer entered on their quest, very badly equipped in this 
respect. They came armed with novelties with new microscopes of 
unprecedented magnifying power, with new stains of great complexity, 
and with new technique of equal elaboration. Instead of first testing 
these inventions on normal tissues, on known morbid conditions, and on 
known microbic diseases, they rushed straight away to the study of the 
minute anatomy of cancer a disease that had never before been investi- 
gated with this degree of elaboration. Although manifesting unfamiliarity 
with the latest findings in normal cytology, they never hesitated as to 
the interpretation of the most obscure and complicated appearances in 
cancer cytology. As to their acquaintance with the life-history and 
histological appearances of microbes, well not to put too fine a point 
upon it this, as a rule, evidently left much to be desired. Approaching 
a subject of this degree of complexity, thus imperfectly equipped, the 
need for control experiments was sufficiently obvious ; yet, as the pub- 
lished reports show, such experiments were seldom made. If, under these 
circumstances, the strange sights thus brought to light in this terra 
incognita were often misinterpreted, what wonder ? The hunt for 
" cancer parasites " has rightly been stigmatized by Schaudinn, as one of 
the most melancholy chapters in biological investigation ; hence, in dealing 
with this kind of publication, we must never forget the need for criticism. 

Passing now to the dominant object of the present chapter, which is 
to review the work done as to the " parastiology " of cancer, it may at the 
outset be mentioned, that microbes first began to be heard of in this 
connexion early in the seventies of the nineteenth century. 

But, long before this, as previously mentioned, 1 similar views had been 
prevalent. At a later period, in the eighteenth century, cancer was 
regarded by John Hunter as the product of a morbid poison, which 
either arose spontaneously or was derived from the contagion of similar 
disease ; and he compared it with small-pox, tubercle, syphilis, and 
similar diseases. 

In 1809, cancer was described by R. Carmichael 2 as : "A parasitic 
disease due to animalculae produced by generatio equivocal He thought 
that carbonate of iron cured the disease, by destroying the animalculse. 



Bacteria. 

In the modern revival, it was among the schizomycetes that specific 
cancer microbes were first alleged to have been discovered. 

Even as early as 1880, Nepveu 3 had described the presence of bac- 

1 Chapter VIII. 

2 An essay on the effects of Carbonate and other preparation of Iron on Cancer, etc. 
Dublin, 1809. 

3 Qaz. Hebd. de Med., etc., 1888, p. 278 ; also C. R. Soc. de Biol., 1887, t, iv., p. 756. 



234 THE NATURAL HISTORY OF CANCER 

teria in tumours of this kind ; and Lebard 1 again called attention to 
this subject in 1885. 

Rappin 2 in 1886, and SchiU 3 in 1887, demonstrated the existence of 
dipiococci in carcinomatous and sarcomatous neoplasms ; and claimed 
that these were the cause of the disease. 

They soon had numerous imitators in Francke, 4 Scheuerlen, 5 Freire, 6 
Lampiazi-Rubino, 7 Sanarelli, 8 Kiibasoff, 9 and others. As, however, 
none of them really succeeded in reproducing the disease by inoculation 
with pure cultures, the futility of their claims for setiological specificity 
soon became apparent ; and they have since been entirely abandoned, 
and have now passed out of recollection. 

At the time of its publication in 1887, however, Scheuerlen's pro- 
nouncement made a great stir. He claimed to have solved the cancer 
problem by the discovery of a specific bacillus, and to have reproduced 
the disease in animals by inoculating them with pure cultures of it. His 
method was that of cultivating the substance of mammary cancers upon 
solid media, comprising sterilized ascitic and hydrocele fluids. On the 
third day, a growth in the form of a colourless film, becoming yellowish 
later usually appeared, which the microscope showed to consist of short 
bacilli and spores. The latter which stained readily with ordinary 
reagents he often found in the .dried juice of cancers ; the former, he 
could not demonstrate in stained histological sections, but he found 
them in fresh cancer-juice. Bitches inoculated in the mammary region 
with pure cultures of these bacilli, developed there in the course of a 
fortnight tumours the size of a walnut. When the animals were killed 
a month after inoculation these tumours were found to be epithelial 
new formations, in which the spores of the bacilli could be easily dis- 
tinguished. 

Senger, 10 Baumgarten n and others, investigating Scheuerlen's bacillus- 
shortly afterwards, showed that it was nothing but a potato bacillus, one 
of the several kinds of organism that grow readily on slices of potato. 
It was therefore a mere epiphyte, having no setiological relation to 
malignant disease. 

Shattock and Ballance, 12 attempting to get cultures from fragments 
of fresh non-ulcerated mammary cancers, removed with aseptic precau- 
tions and carefully transferred to tubes of beef peptone jelly, beef peptone 
agar-agar, and solidified blood-serum, concluded since no growth took 
place in any of the tubes that these tumours contained no microbes 
capable of cultivation. Similar experiments with sarcomatous and 

1 Arch. Gen. de Med., 1885, t. L, p. 413. 

2 " Recherches sur 1'etiologie des tumeurs malignes," Xantes, 1887. 

3 Deutsche med. Woch., 1887, S. 1034. 
* Munch, med. Woch., 1887, Xo. 4. 

5 Deutsche ined. Woch., 1887, Xo. 48, S. 1033. 

6 Bev. d. Cursos. Prat. e. Theor. d. Fac. d. Med. d. Bio de Janeiro, 1889, p. 73. 

7 Li Riforma Med., Xapoli, 1888, vol. iv., p. 20. 

8 Ibid., Roma, 1889, p. 356. 

9 Wien. med. Presse, 1890, Bd. 31, Xos. 29 to 33. 

10 Berlin, klin. Woch., 1888, No. 10, S. 185. 

11 Cent. f. Bakt., etc., 1888, Bd. iii., S. 397. 

12 Transactions of the Pathological Society, London, 1887, vol. xxxviii., p. 412 ; 
also ibid., 1888, vol. xxxix., p. 409. 



THE MICROBIC THEORY OF CANCER 235 

lipomatous tumours, gave the same negative results. Moreover, they 
found that fragments of malignant and other tumours, aseptically 
treated, could easily be kept sterile for considerable periods, just as could 
bits of the healthy tissues. 

Verneuil, 1 having noticed the frequency with which his operation 
wounds became septically infected, after the removal of cancerous 
tumours in which there were areas of softening, made special bacterio- 
logical examination of these foci ; and found that they teemed with 
various kinds of bacilli and micrococci, several species often being present 
in the same tumour. 

In the same year, Zahn 2 by cultivation experiments showed that 
bacteria may abound in the metastases of cancer, even when the latter 
have no direct communication with the surface of the body. 

Hauser 3 thinks we need not be surprised to find bacteria in ulcerated 
malignant growths ; since, under these circumstances, the conditions 
met with are highly favourable to their growth and development. 
When microbes are found in metastatic growths, Hauser believes that 
they are carried there, by tumour elements detached from the primary 
focus. 

Kiibasoff 4 in carcinomata of the stomach found short, thick bacilli, 
which showed active movements when incubated. In various culture 
media such as gelatin, agar-agar etc. they formed scale-like colonies, 
which did not liquefy gelatin. Guinea-pigs, rabbits, cats and dogs, when 
inoculated with pure cultures, died in a comparatively short time. On 
post-mortem examination nodular tumours which are described by 
Kiibasoff as presenting the structure of cancer were found in various 
internal organs. He regarded this bacillus as the true cause of the 
disease. 

Schiitz, 5 by means of various aniline dyes, was able to discriminate 
various forms of bacteria in ulcerated cancer of the lip ; but these he 
regarded as mere epiphytes. 

Richet 6 found septic bacteria often present in cutaneous carcinomata ; 
and extracts made from tumours of this kind seemed to possess a special 
virulence of their own. Thus, while injections of the extract of fresh 
non-ulcerated cancers had no toxic effect whatever on animals, a few 
cubic centimetres of the same preparation from an ulcerating cancer, 
caused convulsions and death. 

Several investigators have reported the existence of bacteria in the 
blood of patients with malignant tumours ; and some have claimed for 
these bodies special setiological significance. 

Hayem, 7 however, who has specially studied the various alterations 
in the form of the blood-corpuscles in malignant and other diseases, con- 
cludes that the pseudo-parasitic bodies are due to degenerative corpuscular 
changes (microcytosis, poikilocytosis, fragmentation etc.). 

Rev. de Chir., 1889, t. ix., p. 793. 

Arch. f. path. Anat., 1889, Bd. cxvii., S. 209. 

" Des cylinder Epitheliom des Magens " etc., Jena, 1890. 

Wien. med. Presse, 1890, Bd. xxxi., S. 1145 et seq. 

Cent. f. Bakt., etc.. 1890, Bd. ix., No. 21, S. 702. 

C. R. de I'Acad. des Sci., 1895. ii.. Xo. 17. 7 " Du Sang," Paris, 1889. 



236 THE NATURAL HISTORY OF CANCER 

Moty x found micrococci in the blood of nearly all the patients with 
sarcoma, examined ad hoc by him. In cultures they developed as a 
narrow, pointed or festooned band, surrounded by small isolated 
colonies. 

Maragliano 2 examined the blood of thirty-three patients with cancer 
of various parts of the body. In nine cases bacteria were present- 
mostly different kinds of staphylococci. In all these instances, the 
tumours showed some signs of disintegrative processes ; but, in none 
of the patients was there any pyrexia, or other indication of septic 
infection. In patients with non-ulcerated tumours, he was never able 
to detect any bacteria in the blood. 

The latest champion of the bacterial origin of cancer is Doyen, of 
Paris ; who, at a meeting of the French Academy of Medicine, held in 
December, 1901, announced the discovery of a new " cancer microbe,"' 
which he called Micrococcus neoformans. He maintains that this microbe 
which is a diplococcus is constantly present in cancerous tumours, and 
may be best demonstrated in sections stained with picro-carmine and 
violet ; and that he has been able to isolate it, and cultivate it, in special 
gelatin-bouillon media. It presented in pairs, and in short chains. He 
found that cultures were more easily obtained from affected lymph-glands 
and secondary growths, than from the primary tumour. He claims to 
have produced cancerous tumours in various animals, by inoculating 
them with pure cultures of the microbe ; and also to have succeeded in 
preparing a sterilized solution of its toxins attenuated in a special 
manner which, when subcutaneously injected into those affected with 
the disease, retards its progress. 

In a subsequent publication, 3 Doyen claims with this solution, up to 
September 30, 1904, to have completely cured 42 out of 242 patients 
treated, and to have markedly benefited many others. 

A committee of the Societe de Chirurgie, which was subsequently 
appointed to report on Doyen's therapeutic methods and results, has 
lately issued an adverse report 4 the unanimous conclusion being, that 
the treatment has no favourable action on cancer : " During the five 
months in which we have examined all the cases which M. Doyen wished 
to show us, we have not seen a single instance of amelioration." 

Jacobs and Geets 5 have since published experiences, which tend to 
support Doyen's thesis ; but Wright and others, who have repeated 
their experiments, have failed to verify their results. 



General Conclusions as to Bacteria. 

From such items as the foregoing, the following conclusions may be 
drawn : 

1. Malignant tumours are singularly prone to bacterial infection, 
owing to their feeble vitality, which is a consequence of defective sanguini- 

1 Bull. Med., October 14, 1894. 2 Gaz. degli Ospitali, January 13, 1901. 

3 " Etiologie et Traitement du Cancer," Paris, 1904. 

4 C. E. Soc. de Chir., July 12, 1905. 5 C. R. Roy. Acad. de Med. Bdgique, 1906. 



THE MICROBIC THEORY OP CANCER 237 

fication. The organisms usually present under these circumstances, are 
such as may be commonly met with in corresponding normal parts of the 
body, e.g., micrococci, diplococci, streptococci, staphylococci, various 
large and small rod-shaped bacilli etc. 

2. In their young and nascent condition, non-ulcerated malignant 
tumours are quite free from bacteria. 

3. Although many kinds of bacteria may find a suitable habitat in 
malignant tumours, none of these organisms fulfil the requirements 
necessary for the establishment of their setiological specificity, as "cancer 
microbes." 

Protozoa. 

Just as the movement in support of the bacterial origin of malignant 
tumours was on the wane, a new movement arose ascribing the causation 
of the disease to parasitic protozoa. 

More than half a century previously, Hake x had noticed that cancer 
cells often contained certain rounded, hyaline, spore-like bodies, which 
he regarded as psorospermial parasites. Some years later, Virchow 2 
also examined these bodies ; but he concluded that they were the out- 
come of endogenous cell formation and degenerative changes. 

About the year 1889, several cytologists (Pfeiffer, Thoma and Darier} 
announced that they had discovered similar bodies which they regarded 
as psorospermial parasites in cancer cells from various parts of the 
body. Thus the old controversy, as to the significance of these bodies, 
was revived ; and this question soon became the cynosure of pathological 
eyes, for the problem of the origin of cancer seemed to concentre in it. 

It appears that Pfeiffer, 3 who had specially studied coccidiosis in the 
rabbit, was one of the earliest to publish an account of parasitic sporozoa 
in human cancer. On teasing fragments of a malignant melanotic 
tumour, on the warm stage of a powerful microscope, he saw plasmodia 
in amreboid movement ; and observed that they resembled one of the 
microsporidia, which infest the roots of cabbages and other cruciferae 
the Plasmodiophara brassicce. 

At about the same time Thoma 4 described certain endocytes, which 
he found in the protoplasm and nucleus of cancer cells ; and he main- 
tained that they were coccidia. 

The announcement by Darier 5 in the same year, of the discovery of 
coccidial parasites in cases of " Paget's disease" of the breast, contributed 
not a little to the general interest which the subject had excited. 

Among the earliest supporters of the protozoan origin of these endo- 
cytes, besides those above mentioned, were Malassez, Albarran, Wickham, 
Metchnikoff, Soudakevitch, Ruffer, Foa and Cattle ; while their non- 
parasitic nature was just as strenuously upheld by Borrel, Cornil, Gibbes, , 
Klebs, Ribbert, Pianese, Delepine, Sroebe, Virchow, Kanthack and others, 

1 " A Treatise on Varicose Capillaries," etc., London, 1839. 

2 Arch. f. path. Anat., Bel. i., SS. 107, 130, 483 ; also Bd. iii., S. 197. 

3 " Die Protozoen als Krankhoitserreger," Jena, 1891. 
* Fortschritte der Med.. 1889, Bel. vii.. S. 413. 

6 C. R. Soc. de Biologic. April 13, 1889. 



238 THE NATURAL HISTORY OP CANCER 

The work of these early investigators was entirely histological ; and, 
it soon became apparent, that they meant to class as cancer parasites, 
every rounded body that was not obviously either an epithelial cell, a 
nucleus, a leucocyte, or a red blood-globule. Indeed, there were some 
among them (Pfeiffer, Adamkiewicz, Jackson Clarke etc.), who went 
to much greater lengths, maintaining that the constituent elements of 
cancerous tumours were merely masses of parasitic protozoa ; and, not 
epithelial cells, as generally believed. In spite of some opposition from 
the more moderate parasitologists, the investigation was continued in 
this spirit, until Soudakevitch l and Ruffer 2 for the first time clearly 
defined precisely what was meant by the term " cancer parasite." They 
thus discriminated from the immense variety of so - called parasites, 
certain small, rounded endocytes, each of which contained a nucleus, 
surrounded by voluminous protoplasm, itself circumscribed by a distinct 
capsule. With the Ehrlich-Biondi stain the nucleus assumed a copper- 
red colour, while the surrounding protoplasm coloured light greenish or 
bluish, the capsule taking a decided reddish tint. Immediately around 
the nucleus a clear zone was noticeable ; and, in " parasites " of a certain 
size, fine radial striation was often seen. All bodies different from these, 
such as had been described by previous observers as cancer parasites, 
Ruffer rejected as such, declaring that they were only pseudo-parasites, 
having no aetiological relationship whatever with malignancy. 

The precise nature and significance of the bodies thus discriminated, 
still remain to be determined. Shattock and Ballance 3 were among the 
earliest of those who undertook experiments, with the object of deter- 
mining whether cancer could be produced by inoculating animals with 
psorospermise from the rabbit's liver etc., as the statements of Darier 
and Wickham implied. Rabbits, monkeys, dogs and rats, were employed 
for this purpose. The method was to scarify the ear, by making one or 
more long incisions on its inner aspect ; and, after bleeding had ceased, 
to rub into the wounds fresh psorospermial material from the liver of a 
recently killed rabbit. This was followed by the formation of linear 
elevations along the incision tracks, owing to reparative hyperplasia ; 
but, otherwise, the results were always negative. This was the case, 
even when large quantities of psorospermial material were injected into 
the jugular vein of dogs etc. 

They concluded that, until animals or human beings had been experi- 
mentally infected by inoculation, with cultures made from Paget's 
disease or from cancerous tumours, nothing could be taken as proved, as 
to there being any causal relation between psorospermiae and cancer. 

According to Adamkiewicz, 4 the infectivity of cancer is so well estab- 
lished, that its parasitic nature may be regarded as a certainty. He 
maintains that the constituent cells of cancerous tumours are not epithelial 
cells, as is generally believed, but parasitic organisms. " A cancer cell 
is not an epithelial cell, but an animal a protozoon especially a cocci- 
cdium (Coccidium sarcolytes}" Since all parasitic microbes produce 

1 Ann. de I'Inst. Pasteur, 1892, No. 3, p. 145 ; also ibid., Xo. 8, 1892, p. 545. 

2 Transactions of the Pathological Society, London, 1893, vol. xliv., p. 209. 

3 Ibid., 189L vol. xlii., p. 377. 

4 " Untersuchungen iiber den Krebs," Wien, 1893, etc. 



THE MICROBIC THEORY OF CANCER 239 

toxins, Adamkiewicz believes that there must also be a special cancer 
toxin ; and this he claims to have discovered in a substance, termed by 
him '' cancroin," which he has extracted from malignant tumours. He 
finds that this substance is chemically akin to neurin " tri-methyl- 
vinyl-ammonium-hydroxide. ' ' 

By implanting brain substance and other tissues from cancer patients, 
into divers regions of various animals, Adamkiewicz claims to have 
caused in them a specialized intoxication, owing to the action of this 
toxin. Xo cultures of any parasitic organism were made. 

Geissler, Kopfstein and others, who repeated these experiments, 
were unable to confirm Adamkiewicz's results. 

By subcutaneously injecting cancer patients with cancroin, Adam- 
kiewicz also claims to have cured many, even after only a few weeks' 
treatment. It must be stated, however, that those who have had the 
best opportunities of closely following his cases, have failed to appreciate 
his alleged curative results ; and, generally, his statements inspire no 
confidence. 

Delepine * found that the psorospermia-like bodies met with in 
malignant tumours failed to respond to any of the chemical tests, which 
give definite reactions with the psorospermial parasites of the rabbit's 
liver. He also failed to find in the so-called " cancer parasites," any of 
the developmental forms met with in the parasitic psorospermise of 
rabbits. 

By inoculating interlamellar films of water, serum, nutrient gelatin, 
and other fluids, with psorospermiae from the rabbit's liver, he obtained 
cultures of these parasites, and succeeded in following their development 
through various stages. By this method, the changes occurring in 
individual psorospermiae could be followed for weeks. 

Delepine suggests that the protozoa-like bodies of malignant tumours, 
should be studied in the same way ; when, if similar changes were observed 
in them, the doubts as to their real nature might thus be removed. 
Attempts subsequently made in this direction by Delepine and Cooper, 
failed to elicit any indications of multiplication and growth when the 
so-called cancer parasites were substituted, in the experiments, for 
psorospermige from the rabbit's liver. 

D'Arcy Power, 2 a supporter of the protozoan theory, has also attacked 
the problem from an experimental standpoint. He brought mucous 
surfaces of rabbits rats, etc. that had for some time been kept in a 
state of chronic irritation, into contact with cancerous tissues, when the 
former became infected with " cancer bodies "; but, cancerous tumours 
could never be thus produced. Only a few experiments were made ; 
and there were no control observations with healthy epithelial, instead 
of cancerous tissues, so that these results are by no means convincing. 

In a subsequent publication (1894), Power admits the validity of this 
criticism ; for, he there says : '' It may be that the " cancer bodies " are 
merely phases in the degeneration of cells. . . . They are met with in 
normal epithelium, which has been slightly irritated ; and, I am there- 

1 Transactions of the Pathological Society, London, 1891, vol. xlii., p. 371. 

2 British Medical Journal, 1893, vol. ii., p. 832 ; also ibid., 1894, vol. ii., p. 638. 



240 p^HE NATURAL HISTORY OF CANCER 

fore boun(} r i to confess myself an unbeliever, in any of the " cancer bodies " 
which ly^ave yet been discovered." 

K'-urloff 1 found an organism, which appeared to be identical with 
thr,o Rhopalocephalus canceromatosus of Korotneff, in a primary cancer of 
/"the skin of the dorsum of the hand of a man aged eighty. 

In a further series of experiments, Shattock and Ballance 2 again 
endeavoured to get cultures of the " parasitic protozoa " of human 
malignant tumours. Under the impression that it might be necessary 
for the hypothetical parasites to pass through some lower organism, in 
order to acquire infective properties for man and animals, they fed worms, 
kept in sterilized sand and water, with bits of mammary cancer. These 
were devoured, but the worms unfortunately died soon afterwards, owing 
to the sterility of the sand depriving them of all other nutriment. Bits 
of fresh mammary cancer were next buried in garden soil, and six weeks 
later these were exhumed and introduced into the abdominal cavity of 
rats ; but only negative results ensued. In other experiments, fragments 
of malignant tumours in Petri dishes etc., were introduced into sterilized 
sand and water to which a little beef peptone broth had been added : 
after variable periods, sand from the vicinity of these bits of buried 
tumour was examined ; but, although the sand often teemed with amoebae 
and bacteria, no sporozoa were present. The results of inoculating 
animals with this sand, and with bits of the tumours that had been 
buried, were always negative. 

Searching for a protective vaccine against malignant disease, Shattock 
and Ballance tried the effect of subcutaneous injections of 50 per cent, 
glycerine extracts of cancer and sarcoma, into patients affected with 
inoperable malignant tumours ; but in no case did any improvement 
ensue. 

They next essayed the effect of injections of the fresh serum of animals, 
such as sheep, which are naturally but little liable to malignant tumours ; 
but these also were inefficacious. The serum of animals into whose 
circulation cancer-juice had been injected, was also employed thera- 
peutically ; but without any appreciable result. 

Bosc 3 endeavoured to get cultures of the hypothetical psorosperms 
of human cancers, by incubating bits of recently removed tumours in 
ordinary culture media. He maintains that the " cancer bodies " 
multiplied in these media ; but, as he never even attempted to inoculate 
animals with the cultures, the value of his statements is comparatively 
small. 

Among those who continued the investigation of the " cancer para- 
sites " discriminated by Soudakevitch and Ruffer, Plimmer 4 was one of 
the first who employed the experimental methods, that had been intro- 
duced by Sanfelice and the Italian pathologists. He seems to have been so 
much impressed by the results of these methods, as even to doubt the 
dictum of Metchnikoff, as to the protozoan nature of these bodies. 

Although Plimmer managed to demonstrate histologically to his 

1 Cent. f. Bakt., etc., Bd. xv., Nos. 10 and 11. 

2 Proceedings of the Royal Society, 1895, vol. lix. 

3 " Le Cancer," Paris, 1898. 

4 Proceedings of the Royal Society, March 9, 1899 ; also Practitioner, April, 1899. 



THE MICROBIC THEORY OF CAXCER 241 

satisfaction " cancer parasites " in almost all of the numerous malignant 
tumours specially examined ad hoc, he only once succeeded in isolating 
by artificial culture " an organism which in certain animals was capable 
of causing death, with the production of tumours in various parts." 
His culture medium was an infusion of human cancer prepared, just as 
the ordinary beef infusion, with the addition, after neutralization, of 
2 per cent, of glucose and 1 per cent, of tartaric acid. 

Guinea-pigs inoculated intra-peritoneally with these cultures, died in 
from thirteen to twenty days ; and on post-mortem examination the 
peritoneum, omentum, liver, spleen, intestines and lungs, were found to 
be studded with small nodules of endothelial structure, the constituent 
cells of which contained " organisms " similar to those isolated from 
the human cancer. He claims that these experiments demonstrate 
" the production of tumours by an organism isolated from human cancer "; 
which, he thinks, " may have a practical bearing on the great question 
of the aetiology of cancer." In some cases he claims to have produced by 
inoculation, true malignant epithelial (cancerous) tumours. Thus, by 
scarifying a rabbit's cornea, and inoculating it with the sediment of a 
ten-days-old culture, he found, when the animal was killed forty-eight 
hours afterwards, that free proliferation of the corneal epithelium had 
taken place, and that these cells were invaded by " cancer parasites." 
This proliferation spread for some distance. Plimmer believed that this 
was an artificially produced cancerous lesion. I certainly think that he 
has not brought forward one iota of evidence, that will justify such a 
conclusion. This lesion migjit just as well have been produced by the 
inoculation of any irritant. Wyss and others have shown that corneal 
lesions of all kinds, involving destruction of surface epithelium, are 
quickly followed by ingrowths of the adjacent epithelial cells, with his- 
tological appearances like cancer. 

In numerous other experiments, rabbits and guinea-pigs were inocu- 
lated intra-venously, intra-peritoneally, and subcutaneously ; but with 
merely negative results. In yet other cases, the only obvious effect was ; 
that the " organisms " were found post-mortem in the blood, internal 
organs etc. 

Pianese * has published a very elaborate study of the cytology of 
cancer, with special reference to the nuclear changes of the morbid cells, 
and to the so-called parasites. He examined specimens from fifty-five 
cancers of different parts of the body. He describes the mitoses found in 
cancers, which he classifies. Special attention is given to the group of 
degenerations which comprises hyalinosis, keratohyalosis, mucoid, colloid, 
and amyloid changes ; and their relations to les corps de Darier, the 
sporozoa of Korotneff (Rhopalocephalus canceromatosus), and to Russell's 
bodies. Endocytes due to secretory changes in glandular cancers are 
also studied. 

Attention is then directed to the nucleus and nucleolus of cancer 
cells ; for, having found that chromatin often occurred in these inclusions, 
Pianese maintained that many of them had a nuclear origin. The 

1 " Beitr. z. Histologie und Aetiologie des Carcinoma " (suppl. Ziegler's Beitr. z- 
path. Anat., Jena, 1896). 

16 



242 THE NATURAL HISTORY OF CANCER 

special nuclear changes may affect chiefly (a) the nuclein (swelling, diminu- 
tion, fragmentation, degeneration) ; (6) the paranuclein (fragmentation, 
degeneration) ; or the nucleolus (vacuolization, encapsulation) ; (c) the 
envelope of the nucleus ; or (d) the nuclear juice (filamentous, nucleo- 
plasmolysis). 

In conclusion, he studied : (1) hyalinosis of the nucleoplasm ; 
(2) pseud-adipose or cystic degeneration of the nucleus ; (3) amyloid 
degeneration of the entire cancerous cell ; (4) necrosis of the nucleus ; 
and (5) amyloid cancer bodies. 

Pianese concludes that, up to the date of his communication (1896), 
we had no evidence, histological or experimental, that would justify us 
in describing any of the numerous " parasites," such as have been figured 
and described as being found in cancers, as other than products of altera- 
tions of the protoplasm, of the nucleus, or of both combined. 

Leyden and Schaudinn, 1 examining ascitic fluid removed from cancer 
patients, made the interesting discovery, that it teemed with rhizopodia 
organisms that had never before been met with in the human body, 
except as parasites of the gastro-intestinal tract. These microbes pre- 
sented as amoeboid bodies, of from 3 to 36 millimetres in diameter, 
their shape being globular or irregularly polygonal, and having a char- 
acteristic appearance, which is compared to a bird's eye. At intervals 
they emitted processes of hyaline ectoplasm, and the pseudo-podia of 
adjacent organisms sometimes anastomosed. Each of them was fur- 
nished with a nucleus of the typical rhizopod type ; and they multiplied 
by segmentation or gemmation, colonies often being formed. One of 
the patients above referred to had cancer of the pylorus ; the other had 
an intra-abdominal tumour. 

When a drop of the ascitic fluid or its centrifugalized sediment, was 
microscopically examined in the fresh state, the organisms were readily 
seen, as above described. Permanent preparations were also made. As 
to the possible setiological relation between these rhizopods and the con- 
comitant cancerous disease, the authors at first declined to commit 
themselves ; but they subsequently affirmed their belief that the organism 
is the specific cancer parasite, although they were unable to comply 
with Koch's postulates ; and they have named it Leydenia gemmipara 
Schaudinn. 

The foregoing publication has been the starting-point of many sub- 
sequent researches. Thus Nils Sjobring, 2 with a culture medium con- 
sisting of nearly equal parts of sterile ascitic fluid and peptone gelatin, 
with the addition of 1-5 per cent, of watery solution of potash soap pre- 
pared with human fat, and 1 per cent, of cane- or grape-sugar, succeeded 
in cultivating from fresh human tumours an animal organism pre- 
senting amoeboid, rhizopod, and involution forms. 

Tubes of this special culture medium were inoculated with pieces of 
non-ulcerating human tumours, that had been aseptically treated ; 
and these were then incubated for a week at 37 C. (98-6 F.). By this 

1 " Sitz. d. Akad. d. Wissenschaft z. Berlin," 1896, Bd. xxxix., S. 13 ; also " Uber die 
parasitare Theorie in der Aetologie der Krebse," Berlin, 1905. 

2 Fortschritte der Mod., 1890, No. 14 ; also Cent. f. JBakt., etc., 1900, xxvii., S. 129. 



THE MICROBIC THEORY OF CANCER 243 

means, from various carcinomata, sarcomata, uterine myomata, and 
ovarian cystomata, Sjobring succeeded in isolating these rhizopod 
organisms. 

With these cultures he inoculated eight white mice, and in four cases 
positive results were obtained. In two cases cultures of human mammary 
cancers, subcutaneously injected, after a period of three months, are 
alleged to have caused the formation of cylinder-celled cancer of the 
cutaneous sweat-glands and hair-follicles. In another experiment, the 
resultant tumour resembled an adenoma of a sweat-gland. In the fourth 
case, a culture from a colloid cystoma of the human ovary, intra-peri- 
toneally injected, gave rise to colloid cystoma of the epididymis etc. In 
all of these animals " cancer bodies," similar to those found in human 
malignant tumours, were demonstrated. With rabbits and guinea-pigs 
the inoculations gave only negative results. 

In their initial stage these " organisms " presented as sarcous, rounded, 
quasi-fatty masses ; subsequently pseudo-plasmodia developed. In cer- 
tain forms the nuclear chromatin could be demonstrated, by aniline blue 
staining and with iron-alum-heematoxylin. Their development was like 
that of the amcebosporoids of the protozoa ; but sexual conjugation, and 
the sickle-shaped germ, were absent. 

Histological sections of the artificially produced skin tumours in mice, 
exhibited at the Congress of German surgeons in 1901, produced a by no 
means favourable impression. The evidence as to epithelial new for- 
mation, was considered to be inconclusive. Juergeiis could not recognize 
the so-called cancer bodies as parasites ; and Israel was of the same 
opinion, maintaining that the so-called sporophoroides and rhizopodia 
were nothing but fat globules and debris. 

Max Schiiller a has published an account of an organism of protean 
form which he detected in carcinomatous and sarcomatous tumours, 
and isolated by cultures. His procedure was that of incubating bits of 
the fresh tumours, taking care not to expose them to a lower temperature 
than that of the body. He discriminates two typical forms ; of these, 
the more characteristic are large organisms, three or four times the size 
of red blood-corpuscles round or ovoid, refractile, of golden yellow or 
brownish colour, having a well-defined capsule perforated by numerous 
pores, within which are three or four small protoplasmic masses, which, 
in the course of development, appear to escape through the capsular pores 
and form independent organisms. It is from the latter that the smaller 
type of organism is believed to originate ; these present as clear or finely 
granular, rounded cells of golden colour. These small forms act as intra- 
cellular parasites, penetrating the tumour cells, even to their nuclei, where 
they undergo their further phases of development identical parasites 
being found in both the epithelial and connective-tissue forms of malignant 
disease. 

In living, hanging - drop cultures, these organisms present fine 
peripheral processes. It is believed that the small types of organism 
develop into the larger ones. 

1 " Die Parasiten im Krebs und Sarkom des Menschen," Jena, 1901 ; also abstract in 
Cent. f. Bakt., etc., 1900, Bd. xxvii., S. 511. 

162 



244 THE NATURAL HISTORY OF CANCER 

Cultures injected into the tissues and organs of rabbits and other 
animals, caused local proliferations, similar to those met with in com- 
mencing cancer carcinomatous cultures being capable of producing 
sarcomatous etc. 

Max Schiiller has also found and made cultures of similar organisms, 
from the lesions of acquired and congenital syphilis. 

Not a little sensation was caused when, in 1901, Volcker l declared 
that Max Schuller's large yellow, cancer parasites, were in reality nothing 
but cork cells ; which had got into the specimens, through the medium of 
the oil used for clarifying the same. 

According to Hansemann, 2 the endocytes of cancer cells are derived 
from many different sources, which he enumerates as follows : (1) De- 
generations of cells and secretory anomalies, (2) phagocytosis, (3) invagi- 
nation, (4) abortive and pathological mitoses, (5) special organs of cells, 
e.g., archoplasm and centrosome, (6) extra-cellular hyaline drops (Russell's 
bodies), and (7) cancer cells themselves. 

In a previous chapter I have referred to the observations of Borrel 
and Le Count, as to the identity of Ruffer's endocytes with the archo- 
plasm and centrosome. 

Olt 3 considers that the so-called parasites of cancer are, in reality, 
red blood-cells in various stages of degeneration. He attempted to obtain 
cultures from cancers from the horse, dog etc., using various media. 
The results were negative. He concludes : " From the fact that these 
supposed parasites are iron-containing bodies, and that their optical 
properties are very similar to those of the red blood-cells, it may be 
inferred that the latter are concerned in their formation." Sjobring's 
rhizopod parasites, Olt regards as nothing but particles of free fat. 

Bruandet 4 by injecting a solution of coccidia into the pelvis of the 
kidney of a rabbit, after having ligatured the ureter lower down, claims 
to have caused thereby quasi-cancerous epithelial changes in the kidney, 
as determined by histological examination, when the animal was killed 
about three and a half weeks after the injection. 

Gaylord 5 claims to have discovered " the protozoan of cancer," in 
ascitic fluid derived from a patient with colloid cancer of the peritoneum ; 
which, when inoculated into animals, produced cancerous tumours. 
Cultures of this organism on Fucus crispus bouillon gave similar results. 
He also found microbes of this kind, in various cancerous and sarco- 
matous tumours ; and got pure cultures of them. In advanced cases, 
they could always be detected in the patient's blood, and in the internal 
organs. With cultures from these various sources, many animals were 
inoculated ; and, in a few instances, nodular tumours were found a month 
or so later, when the animals were killed. In an experiment in which the 
injection was made into the jugular vein of a guinea-pig, a pulmonary 
nodule was found, when the animal was killed three and a half weeks 
later. Microscopical examination of this artificially produced tumour, 
revealed proliferous cells in branching columns, which Gaylord interpreted 

1 Deutsche med. Woch., July 25, 1901. 2 Berlin, klin. Woch., 1894, No. 1. 

3 Deutsche thierdrzt Woch., 1900, Nos. 22 and 23. 

* La Presse Mid., 1902, p. 400. 

6 Journal of the American Medical Association, 1901, vol. cxxi., p. 503. 



THE MICROBIC THEORY OF CANCER 245 

as adeno-carcinoma. For the demonstration of this protozoon, Gaylord 
relies chiefly on unstained specimens the scrapings of cancerous tumours 
etc. He found the parasites in every case of cancer and sarcoma specially 
examined, as well as in myoxma, fibro-adenoma, colloid goitre, and syphi- 
litic glands. It is evidently very similar to the bodies previously described 
by Schaudinn and Sjobring, and to Max Schiiller's " young forms." In 
the fresh state, Gaylord's parasite closely resembled fatty gloubles ; 
indeed, it was only by finding that they did not react with ether and 
osmic acid as fat does, that he was able to discriminate them from fatty 
aggregations. He next found, that he could crack their edges with a 
cover-glass. They existed in greatest abundance, in the softened dis- 
integrating areas of cancerous tumours, where Plimmer and Ruffer could 
never find parasites. 

Gaylord maintains that there is great resemblance between his cancer 
parasites ; and the bodies met with by Pfeiffer and others, in variola 
and vaccina, which are also believed to be protozoa. They present as 
pale yellowish, granular bodies, like fat droplets, from 3 to 10 millimetres 
in diameter, large and small types being discriminated. By incubating 
hanging-drop preparations of fresh cancer-juice, derived from scraping 
the tumour, the smaller forms of the organism could be followed in their 
development ; they augmented in size and became granular, emitting 
pseudo-podia and developing a nucleus, ultimately being converted into 
sporiferous sacs. 

Feinberg l claims, as the outcome of histological research with special 
staining, to have discovered a new intra-cellular sporozoan cancer 
parasite (Histosporidium carcinomatosum), which he maintains solely on 
the histological appearances is the true cause of the disease. It is in 
the nucleus of this parasite, and in its staining reactions, that Feinberg 
finds the distinctive features requisite for the recognition of the same. 
Outside the body, he believes this organism only exists in the spore form. 

Otto Schmidt 2 claims to have discovered a protozoon-like parasite in 
malignant tumours, which he has cultivated outside the body ; white 
mice, injected with these cultures, developed malignant tumours. He 
has found this parasite in animal, as well as in human, malignant tumours. 
Dead cultures of this organism, and the serum of animals immunized 
by culture inoculations, were found to exert protective action against 
malignant growths. Schmidt also claims to have cured many persons 
affected with cancer, by means of similar inoculations ; and greatly to 
have benefited still more. 

This supposed cancer specific has been tested at the Middlesex 
Hospital ; 3 but, none of the patients there treated, derived any benefit 
from the procedure. 

It has been pointed out, that the " cancer parasites " described 
by Leyden, Sjobring, Schiiller, Gaylord, Feinberg and some others, 
much resemble the Plasmodiophora brassicce, a parasitic organism, which 
causes tumour-like swellings (club-root) in cruciferous plants. As pre- 

1 Wien. klin Woch., 1903, No. 45, S. 1235; also "Des Gewebe und die Ursache der 
Krebsgeschwiilste," etc., 1903. 

2 " Mittheilung aus Dr. O. Schmidt's Laboratorium," 1905. 

3 Arch. Middlesex Hospital, 1904, vol. iii. (J. W. G. Myler). 



246 THE NATURAL HISTORY OF CANCER 

viously mentioned, Pfeiffer, who first described the endocytes of cancer 
as parasitic protozoa, long ago called special attention to this similarity. 
This organism lives symbiotically in the infected plant-cell, its spores 
being found even within the nucleus ; and thus it is believed that the 
abnormal local cell proliferation is excited, which results in the formation 
of the tumour-like excrescences. It is claimed that, just as these plant 
formations are caused by the plasmodiophorae ; so human cancers are 
caused by parasitic intra-cellular protozoa. To test this conception, 
Podvyssotski J has struck out a new line, by experimenting with this 
organism, which is a kind of myxo-myces. He inoculated rabbits, rats, 
guinea-pigs etc., with these parasites, producing granulomatous forma- 
tions " myxo-mycetic perithelioma," but not epithelial proliferation. 
Within the cells of these artificially produced tumours, he found spores 
of the plasmodiophora ; in such vicinities there were also many giant 
cells, and evidences of phagocytosis. These nodular formations were, 
however, evanescent. 

Gaylord 2 has also made experiments of this kind. Thus, with fresh 
" club-foot " material, various animals were inoculated ; and, when these 
were killed on the twelfth day after the experiment, granulomatous 
nodules were found, which comprised many phagocytic cells, in which 
were spores and spore cysts. There was also some infiltration of the 
surrounding tissues with leucocytes. The histological appearances of 
these spores were often, " indistinguishable from those of cancer inclu- 
sions "; but there were no signs of epithelial proliferation, nor of any struc- 
ture like cancer. According to Gaylord, these artificially produced 
nodules were true grafts their cells being derived exclusively from the 
cells experimentally implanted. 

Tuboef 3 inoculated many animals with this same parasite ; but pro- 
duced nothing at all like cancer. 

Robertson and Wade 4 claim to have proved by histological methods, 
that cancerous tumours comprise intra-cellular parasites, which are 
identical with the Plasmodiophora brassicce in its pre-spore, spore, pre- 
amoeboid and amoeboid stages ; but much more minute. The reactions 
of these bodies with the platinum and silver-gold methods, were iden- 
tical with those given by the " club-foot " parasites. They also claim 
to have grown from cancerous tumours, an organism which represents 
the post-spore or pre-amceboid stage of a plasmodiophora ; and they 
maintain that this organism has the same relation to cancer, as the 
Plasmodiophora brassicce has to " club-foot "; that is to say, is its specific 
causative factor. No inoculation experiments are reported. Alto- 
gether, the authors' conclusions seem to go beyond what is warranted 
by the ascertained facts. In view of the cloud of adverse witness set 
forth in the preceding narrative, as well as in what follows, the futility 
of claims to determine the nature of cancer endocytes, solely by histo 
logical methods, ought by this time to be generally recognized. 

1 La Presse Med., 1900, p. 77. 

2 Fourth Annual Report of the Cancer Laboratory, New York State Board of Health, 
1902-1903, p. 20. 

3 " Verhandl. d. Komites f. Krebsforschung," S. 74, Berlin, 1902. 

4 Lancet, 1904, vol. ii., p. 469 ; also ibid., 1907, vol. ii., p. 358. 



THE MICROBIC THEORY OF CANCER 247 

In a recently published account of " further researches," the authors 
claim to have confirmed their previous findings ; and the parasite is now 
identified as " Spirochceta microgyrata." Thus a spirochaetan origin of 
cancer is suggested. 

As Lubarsch has well said, those who claim that these endocytes are 
parasites, must not only prove that they resemble known parasites ; 
but also that they cannot be anything else. The need for insisting on the 
strict observance of this wholesome precaution is emphasized, by the 
recollection of the innumerable diverse interpretations, that have been 
placed on these appearances by equally competent workers ; some of 
whom (e.g., Plimmer and Sawtchenko) have even regarded the very 
same bodies at one time as protozoa, and at another time as blasto- 
mycetes etc. 

Very thorough investigations as to the nature of the special " bird's- 
eye " cell inclusions, described by Soudakevitch, Ruffer and Plimmer, as 
typical of the protozoan cancer parasite, have lately been made by 
Greenough, 1 Nosske, 2 and Honda. 3 All the above are agreed that these 
endocytes are not parasites ; but secretory products, formed in cells of 
glandular origin cancerous as well as non-cancerous (e.g., chronic 
cystic mastitis, fibro-adenoma etc.). They dispute the contention of 
Plimmer and Gaylord, that inclusions of this kind are met with in all 
malignant tumours, having found them absent in epidermoidal cancer of 
the skin and in sarcoma. 

Blum, 4 the latest student of this matter, finds no reason for regarding 
these bodies as parasites ; and maintains that there is no evidence to 
connect them, in any way, with the causation of cancer. 

Of a large number of culture experiments made in various media, 
with cancerous tissue, 0. Richardson 5 was unable to cultivate from the 
morbid tissues and fluids, any specific infecting organism. 



General Conclusions as to Protozoa. 

Before entering on any discussion as to the setiological significance 
of the hypothetical protozoa of malignant tumours, we want to be 
reasonably assured that such parasites really exist in these tumours. 
Hence, it is to this aspect of the question, that we must first of all 
direct our attention. 

It will be gathered from what has been stated, that the evidence 
hitherto adduced is almost entirely histological ; for, the results of so- 
called cultures and of inoculation experiments, in this connexion, have 
established nothing definite. 

Even if pathologists were unanimous in interpreting the appearances 
revealed on microscopical examination of malignant tumours, as indica- 

1 Third Report of the Croft Cancer Commission of Harvard Medical School, 1905, 
p. 29. 

2 Deutsche Ztits. f. Chir., 1902, Bd. Ixiv., S. 352. 

3 Arch. f. path. Anat., 1903, Bd. clxxiv., S. 96. 

4 Ibid., 1905, Bd. clxxix., S. 475. 

. * Second Report of the Croft Cancer Commission of Harvard Medical School, 1902, 
p. 46. 



248 THE NATURAL HISTORY OF CANCER 

tive of the presence of protozoa ; in the absence of corroborative evidence, 
such unanimity would fall far short of scientific proof. But, when we find 
that most pathologists decisively reject this interpretation, maintaining 
that the bodies which have been thus described are not parasites at all, 
but merely products of the biological changes often degenerative 
incidental to the life of the part, secretory products, derivatives of the 
nuclei or protoplasm of the tumour cells, of leucocytes, of red blood- 
globules etc. ; the futility of relying on the appearances revealed by the 
microscope, for the proof of the presence of parasitic protozoa in malignant 
tumours, becomes apparent. 

It is passing strange, that those who are so insistent on maintaining 
the protozoan nature of certain appearances revealed by the histological 
examination of malignant tumours have, with singular unanimity, failed 
to make control observations. Had they done so, they would have found 
similar appearances often present in various non-cancerous conditions, 
e.g., in chronic cystic mastitis, in mammary adenoma etc. (Greenough) ; 
in variolous and vaccinal lesions (Pfeiffer, Guarnieri, Mann etc.) ; in 
healing wounds, and after artificial irritation (Spirlas, Pierallini, D'Arcy 
Power, Galeotti etc.) ; in syphilitic lesions, herpes, endometritis, mycosis 
fungoides etc. 

Moreover, in undoubted cases of human psorospermosis, such as 
those described by Leuckhart, Albarran, Keen, Silcock, Eve, and others, 
the lesions met with bore no resemblance whatever to malignant disease. 
Similarly in animals (rabbits etc.), the lesions caused by these parasites 
never present any of the special features of malignant tumours. 

It accords with this, that tumour cells containing " parasitic protozoa" 
always appear to be in a state of degeneration ; and to be incapable of 
that active proliferation, which is an essential feature of malignancy. 

Again, the chemical reactions of malignant tumours are very different 
from those of lesions in which psorospermia abound ; for, they contain 
neither chitin, cellulose, nor albumose (Brodie, Hewlett). On the other 
hand, they are rich in glycogen ; which, according to Brault, is absent 
from parasitic pseudo-plasms. Moreover, " falciform bodies " have never 
been demonstrated in the so-called psorospermia of malignant tumours ; 
and no alkaloid has ever been separated from them. 

Before such bodies as those described by Schaudinn, Sjobring, Max 
Schiiller, Gaylord, Feinberg, Robertson and Wade, can be accepted as 
parasitic protozoa, the possibility of their being derivatives of pre- 
existing somatic structures must be negatived. 

The more carefully the subject is considered, the clearer it appears ; 
that the " protozoon of cancer " has failed to make good its entity. 
This hypothetical microbe appears to be a mere figment of the imagina- 
tion, which has been projected into the field of observation, in consequence 
of errors of diagnosis : it is a case of mistaken identity. 

In this opinion, modern zoologists are at one with pathologists ; thus 
Doflein, 1 the latest investigator of the protozoa, says : " The zoologist 
cannot at present admit, that any one of the so-called cancer parasites, 
is a protozoon." 

1 "Die Protozoen als Parasiten und Krankheitserreger," Jena, 1901. 



THE MICROBIC THEORY OF CANCER 249 



Blastomycetes. 

The third great movement in connexion with the microbic origin of 
malignant tumours was originated by Russell, 1 who (in 1890) detected 
certain " fuchsin bodies " in cancerous tumours, which he regarded as 
the characteristic organisms of cancer ; and these he believed to be para- 
sitic blastomycetes, of the same order as the yeast fungi. It cannot be 
said that Russell's views met with much support, until some years 
later, when the Italian pathologists took the matter up ; and, by means 
of experimental methods, aroused fresh interest in the subject. 

It is especially owing to the work of Sanfelice, 2 Director of the Hygienic 
Institute at Cagliari (Sardinia), that so much attention has centred on 
the blastomycetes in this connexion. Moreover, he removed the study 
of the subject from the histological to the experimental region. It 
appears that, even as early as 1895, he was engaged in studying certain 
organisms found in infusions of various kinds of fruits ; and, in so doing, 
he was struck with the resemblance which some of them presented to 
the so-called " fuchsin " bodies, found by Russell in human cancerous 
neoplasms. Of these organisms he obtained pure cultures, with which 
he proceeded to inoculate the tissues and organs of various animals. He 
thus found that some of them were pathogenic, the effect varying in 
different animals. In many animals nodular swellings were produced 
at the seat of inoculation, in adjacent lymph-glands, and sometimes in 
more distant parts, which he thought might not unfairly be compared 
with human malignant tumours. 

Sanfelice had no doubt that the organisms he experimented with were 
blastomycetes ; and, the pathogenic form, he discriminated as Saccharo- 
myces neoformans. In most cases, the tumours thus produced were 
nothing but inflammatory pseudo-plasms. But, with cultures of a microbe 
of this kind, isolated from a fermenting infusion of lemon-skin, he claims 
to have produced, by inoculation, malignant epithelial neoplasms 
(cancers) in dogs. 

When these cultures were injected into the peritoneal cavity, nodular 
formations at first resulted ; from these fresh cultures were made, and 
after the microbe had thus been passed through several dogs, it was 
found to have acquired increased virulence. 

Of thirty dogs inoculated with cultures thus produced, in two Sanfelice 
claims to have caused true epithelial cancer. 

In the case of a bitch inoculated in the posterior mammary region, 
there was considerable tumefaction at the seat of inoculation one month 
afterwards. The animal then became cachectic, and died ten months 
after inoculation. Besides the mammary tumour, post-mortem examina- 
tion revealed enlargements of the adjacent inguinal and abdominal 
lymph-glands. Histologically examined, all of these tumours showed 

1 British Medical Journal, 1892, vol. ii., p. 1356. 

2 Cent. f. Bakt., etc., 1895, Bd. xvii., S. 113 and 625; Bd. xviii., S. 521; Bd. xxiii., 
SS. 155 and 276 ; and Bd. xxi., 1902, S. 254. Also series of articles in Zeits. f. Hygiene 
und Infections-krankheiten, 1895, Bd. xxi., SS. 32 and 394 ; Bd. xxii., 1896, S. 171 ; 
Bd. xxvi., S. 298 ; Bd. xxix., 1898, S. 463. 



250 THE NATURAL HISTORY OF CANCER 

the structure of glandular cancer. Numerous " parasites " were present 
in them, but no cultures could be obtained. The latter defect is unfortu- 
nate, as the possibility of the animal having been previously affected 
with mammary cancer, to which bitches are exceedingly prone, thus 
cannot be excluded. 

A similar defect characterizes the other positive result ; when, after 
inoculation of the testes, a secondary tumour formed in the penis. 
Sanfelice also claims to have isolated blastomycetes from human 
malignant tumours ; but, when cultures of these organisms were injected 
into various animals, no tumour formation ensued. 

In a recent publication x Sanfelice still claims, that he can produce 
malignant tumours in animals, by inoculating them with blastomycetes 
and their soluble products. 

Roncali, 2 investigating the subject chiefly from the histological stand- 
point, has detected in human cancers and sarcomas intra- and extra- 
cellular bodies, similar to those described by Sanfelice. He is convinced 
that these bodies are parasitic blastomycetes. 

With Sanfelice, in 1898, he succeeded in isolating similar organisms 
from human cancerous tumours, which they found to have pathogenic 
properties ; but, when these were injected into certain animals, only 
pseudo-inflammatory, tumour-like swellings resulted. These cultures 
were made with difficulty, and they soon lost their virulence, so that 
nothing further was accomplished in this direction. 

At the meeting of the Italian Surgical Congress, in 1900, Roncali 
again took up this question. He described the appearances found on 
histological examination, of an intra-cranial fibre-sarcoma of the dura 
mater. This tumour teemed with parasitic blastomycetes. After 
having fully described their morphological features and their precise 
localization in the tumour, which were such as clearly indicated genetic" 
correlation, he arrived at the following conclusions : (1) This case proved 
that blastomycetes could not be mere accidental epiphytes in malignant 
tumours. (2) Although he failed to isolate and cultivate blastomycetes 
from the tumour, this was no proof that they did not exist, nor did it 
imply that they were products of degeneration ; for, as Sanfelice had 
shown, when the parasites assumed the form of " Russell's bodies," 
they were no longer cultivable. (3) Provided one knew how to recog- 
nize them, and had the patience to search for them, these parasites could 
always be found in malignant tumours. (4) The so-called parasitic 
protozoa and coccidia, described by other investigators as being con- 
stantly present in malignant tumours, were nothing but blastomycetes, 
as the author has maintained ever since 1895. (5) Blastomycetes were 
the real setiological factor of malignant tumours (epithelioma and sar- 
coma), as Sanfelice had experimentally demonstrated. 

In the interesting discussion which followed the reading of Roncali's 
paper, Bastianelli maintained that it was not sufficient to have stained 
and described these bodies, to prove that they were blastomycetes. It 

1 Annali d'igiene sperimentali, 1907, vol. xvii. 

2 II Policlinico, October 1, 1895; and ibid., October 31, 1896 (suppl.): also Cent. f. 
Bakt., etc., 1895, Bd. xviii., Heft 12-15 ; ibid., 1898, Bd. xxiv., Abth. i., S. 61. 



THE MICROBIC THEORY OF CANCER 251 

was necessary to give this proof, which the author had not done. Biondi 
said that of all the researches hitherto made in connexion with the para- 
sitic origin of malignant tumours, the only really important facts hitherto 
obtained, were the two positive results announced by Sanfelice ; and these 
undoubtedly gave food for thought. 

Durante could not support the blastomycetic theory of the origin of 
malignant tumours, because the precise conditions which would enable 
him to say that the blastomycetes were really the causal factor were 
wanting. Sanfelice's experiments were lacking in this respect. He had 
seen his specimens ; but was not convinced as to the epithelial nature of 
the experimentally produced tumours. 

Maffuci and Sirleo, 1 as the result of numerous inoculation experi- 
ments on various animals, and of many culture tentatives with human 
malignant tumours, sum up their conclusions as follows : (1) On a priori 
grounds, the infective origin of malignant tumours is probable. (2) The 
infective agent has not yet been determined, by either histological or 
experimental researches. (3) Investigations relating to the infective 
agents of tumours, should not be limited to one class of parasites. 
(4) Among the blastomycetes, some have pathogenic properties. (5) The 
lesions induced by blastomycetes, are quite different from such new 
growths as carcinoma and sarcoma. (6) Pathogenic blastomycetes may 
induce septicaemia, suppuration, and chronic inflammatory changes of 
granulomatous nature. (7) Blastomycetes found in human malignant 
tumours, when inoculated into animals, have hitherto producd only 
ordinary inflammatory pseudo-plasms. The authors deny that malignant 
epithelial tumours can be produced in dogs, by pure cultures of blasto- 
mycetes, as Sanfelice alleges. (8) In human cancerous and sarcomatous 
tumours blastomycetes cannot always be demonstrated, either histo- 
logically or by culture. (9) In ulcerating human malignant tumours, 
blastomycetes may be found. (10) The conditions under which this 
happens, and the distribution of the blastomycetes, are such as lead to 
the inference that the infection has been superadded. (11) While not 
denying the possibility that blastomycetes may cause malignant tumours, 
the authors maintain that this has not been proved experimentally. The 
tumour-like swellings produced in animals, by inoculation with pure 
cultures of blastomycetes, are inflammatory pseudo-plasms (granulo- 
mata), and never true malignant tumours. 

Corselli and Frisco 2 isolated and obtained pure cultures of blasto 
mycetes, from a sarcomatous tumour of the mesenteric glands of man 
With these cultures they inoculated guinea-pigs, rabbits, and dogs ; 
and in several of the animals thus experimented on, they claim to have 
produced similar sarcomatous growths. 

Even before the Italian pathologists took the matter up, several well- 
marked instances of blastomycetic infection in humanity had been 
reported. 

1 Arch, ed atti. d. Soc. Ital. di Chir., Roma, 1897, vol. xi., p. Ixvii. ; also Cent. f. Path, 
u. path. Anat., 1895, Bd. iv., S. 305 ; Bd. vi., S. 438 ; also Zeits. /. Hygieneu. Infections- 
krankheiten, 1898. Bd. xxvii., S. 438 ; and II Policlinco, vol. v., May, 1895. 

2 Cent. f. Bakt., etc., 1895, Bd. xviii., Heft 12 and 13. 



252 THE NATURAL HISTORY OF CANCER 

Thus, Busse, 1 in 1894, published the case of a woman, aged thirty-one, 
with a suppurating pseudo-sarcomatous tumour of the tibia, of slow 
growth ; in which he found, in the primary as well as in the secondary 
swellings, numerous blastomycetes, as determined histologically and by 
experimental inoculation of animals therewith. Pure cultures of these 
were also made ; and when rabbits, dogs, rats etc., were inoculated with 
them, suppurative local swellings resulted. In white mice these inocula- 
tions caused death, and the fungi were demonstrated in the animals' 
blood. Intra-peritoneal inoculation of rats, resulted in the production 
of enormous tumours, which often generalized. 

The patient above referred to, who presented other signs of general 
blastomycetic infection, died thus thirteen months after softening of the 
tibial tumour, in a state of extreme marasmus. Besides the tibial 
tumour, similar swellings had formed over the sixth left rib and over 
the right ulna. At the necropsy, there was general enlargement of the 
lymph-glands, besides softening nodules in the spleen, kidney and lung. 
Histologically examined, all of these lesions teemed with blastomycetes, of 
which cultures were made, which succeeded best on potato. Besides these 
microbes, the tumour-like swellings comprised numerous giant-cells, and 
much immature connective tissue, with pus-cells etc. 

Kahane 2 also demonstrated and made pure cultures of blastomycetes, 
from cancers of the uterus etc. ; and, in some cases of this kind, he claims 
to have seen similar parasites in the blood. 

Curtis 3 of Lille has recorded the history of a soldier, with a large, 
soft, pseudo-myxomatous tumour in the upper part of the thigh, which 
clinically resembled sarcoma. There was another similar tumour in 
the lumbar region. These tumours were situated in the subcutaneous 
tissue. When laid open, the groin tumour looked like myxo-sarcoma. 
Histologically examined, large parts of it were comprised almost entirely 
of masses of blastomycetes extra- and intra-cellular supported by a 
vascular connective-tissue network. The tumour substance had con- 
tagious properties ; for, a fragment of it implanted into a rabbit in the 
course of ten days gave rise to a tumour, the size of a small orange, 
which also teemed with yeast-like fungi. The organism grew rapidly 
on potato and gelatin, multiplying by gemmation ; and it is named by 
the author Megalococcus myxoides. The injection of pure cultures into 
white rats and mice, caused tumours like those in the soldier to form 
at the seat, of inoculation, with metastases in internal organs etc. 

These experiments by Busse and Curtis, taken in conjunction with 
those by Sanfelice and his followers, show that for mankind and animals, 
certain yeasts may give rise to quasi-malignant pseudo-plasms. 

Monsarrat 4 claims to have isolated an organism from cancer, grown 
in various media, and to have inoculated animals with pure cultures of 
it, causing in them endotheliomatous new growths, whence the parasites 

1 Cent. f. Eakt., etc., 1894, Bd. xvi., S. 175 ; also Arch. f. path. Anat., 1895, Bd. cxl., 
S. 23; and ibid., 1896, Bd. cxliv., S. 360. 

2 Cent. f. Bakt., 1894, Bd. xv., S. 629 ; and Bd. xviii., S. 616. 

3 Ann. de I'Inst. Pasteur, 1896, t. x., p. 448. 

4 Proceedings of the Royal Society, 1900, vol. Ixvi., p. 58; also Liverpool Med.- 
Chir. Journal, 1900, vol. xx., p. 318 ; and Transactions of the Pathological Society, 
London, 1905, vol. Ivi., p. 272. 



THE MICROBIC THEORY OF CANCER 253 

were recovered. These bodies were identical with the blastomycetes 
described by Sanfelice. Cultures were difficult to obtain ; for, of twenty- 
seven mammary cancers systematically examined, only one yielded a 
positive result. The organism grew but slowly on ordinary media. In 
six cases he examined the blood of patients with advanced cancer, but 
in all the results were negative. Monsarrat's cultures soon lost their 
virulence, and became inert. Attempts to sustain or increase their 
pathogenic properties, by successive passage through guinea-pigs and 
other animals, were unsuccessful. In his latest publication (1905), 
Monsarrat maintains that this organism is the specific cause of mammary 
cancer, and by injecting it into guinea-pigs and dogs, he claims to have 
caused cancerous tumours in them ; but, a committee of the London 
Pathological Society having examined his specimens, found in them 
" nothing suggestive of carcinoma." 

Leopold l found blastomycetes in non-ulcerated cancers from different 
parts of the body. Of twenty such tumours examined, he obtained 
cultures from four. His best material was derived from ovarian cancers. 
A special feature of his work is the prolonged study he made of particles 
of cancer substance in hanging drops of sterile bouillon, in a specially 
constructed thermostatic microscope. In these preparations, some of 
which were preserved for 200 days or more, blastomycetes were seen in 
various stages of development ; and their multiplication by budding 
was studied. The organisms isolated from all of these four cancers, 
caused glucose to undergo alcoholic fermentation. In fixed preparations, 
double-contoured and budding organisms, as well as round bodies, were 
found ; and there could be no doubt as to their being blastomycetes. 

The following experiments on animals were made : (1) A small 
piece of fresh human cancer was implanted into the abdomen of a rabbit, 
with aseptic precautions : on the death of the animal, four years and five 
months afterwards, there was found a suppurating tumour in the abdo- 
men and epithelial overgrowths in the lung. (2) Fresh cancer substance 
implanted in the abdomen of a rat was followed by death, with the pro- 
duction of " adeno-sarcoma " in the right groin. (3) A pure culture from 
cancer of the human ovary, injected into the testis of a white rat, caused 
the formation of a sarcomatous tumour at the seat of inoculation and of 
multiple sarcomata (myeloid and round-celled) in the abdomen. 

In the material injected, blastomycetes were present ; similar organisms 
were found in the experimentally produced tumours, from which pure 
cultures were again secured. 

A curious feature of these experiments was the production of sarcoma 
in animals, with organisms derived from human carcinomata. 

Of fifteen human malignant tumours removed with the strictest 
aseptic precautions, and examined for blastomycetes, Carini 2 got only 
one successful culture. This, he thought, was probably a contamination 
product. He never succeeded in producing a malignant tumour, by the 
injection of pure cultures into animals. Histological examination of 
forty-four human tumours (mostly malignant), showed the presence of 
" Russell's bodies " in eighteen. Similar bodies were found in non- 
1 Arch. f. Gyndkologie, 1900, Bd. Ixi., S. 77. 2 II Policlinico, AprU 15, 1900. 



254 THE NATURAL HISTORY OF CANCER 

malignant tumours, and even in normal structures, such as the prostate. 
He considered that the staining reactions of these bodies were not really 
characteristic of blastomycetes. 

Petersen and Exner, 1 experimenting on animals with Sanfelice's 
Saccharomyces neoformans and other blastomycetes, found that the 
cultures produced large nodules at the seat of inoculation, with secondary 
formations in the kidney, spleen, lungs and lymph-glands. None of these 
formations presented the structure of human cancer or sarcoma they 
were rather granulomata, comprising many giant-cells and masses of the 
parasites. From the histological examination of many specimens, they 
concluded that the endocytes of human malignant tumours are very rarely 
due to parasites. 

Cultures of yeasts from malignant tumours so seldom occur, that the 
few successful results may be ascribed to accidental contamination. 
Those animal and human diseases that have been recognized with cer- 
tainty, as due to yeast infection (cutaneous ulcers, inflammatory swellings, 
endometritis, abscesses etc.), have no resemblance whatever to cancer. 
The tumour-like lesions produced by yeast inoculations are granulomata, 
and not true tumours. 

Wlaeff and Weinberg 2 repeated Sanfelice's inoculation experiments, 
but failed to produce any tumour having the least resemblance to cancer 
or sarcoma. As a rule, only granulomatous swellings resulted ; but, in 
a few cases, pseud-adenomatous, cyst-like, and papilliferous, formations 
followed. Wlaeff was able to exalt the virulence of pathogenic blasto- 
mycetes, by repeated passage through animals. Cultures thus treated 
produced different results when inoculated into various animals ; in 
some they caused septicaemia, in others local swellings and cysts, and in 
guinea-pigs a cutaneous lesion like lupus vulgaris. Weinberg found that 
the cysts produced by injection of feebly virulent cultures, contained 
numerous more or less degenerate blastomycetes, the cyst wall being of 
inflammatory origin. Wlaeff isolated blastomycetes from the juice of 
a sarcoma of the human uterus, and obtained pure cultures of them. He 
also demonstrated their presence histologically in the tumour. 

In subsequent publications, Wlaeff 3 concluded that, since numerous 
investigators have isolated blastomycetes in pure cultures from malignant 
tumours, and have by inoculation with these produced infective growths 
in animals, these organisms are the causative agents of malignant disease. 
For various non-malignant tumours (adenoma, fibroma, cysts etc.), he 
advocates a similar aetiology. 

He prepared a serum for inoculating animals against malignant 
disease, and found that in rats and monkeys, it conferred protection 
against growths caused by blastomycetes. Wlaeff subsequently used 
this serum, for the treatment of sixty cases of human malignant tumours ; 
and came to the conclusion, that, when it was injected early, before 
lymph-gland dissemination had supervened, it had a curative effect. 

1 Beitrage z. klin. Chir., 1899, Bd. xxv., S. 769. 

3 Butt, et mem. de la Soc. Anat. de Paris, t. Ixxiv., 1899, pp. 706 and 842; also ibid., 
t. Ixxv., 1900, p. 147 ; also C. JR. Soc. de Biologie, 1900, lii., p. 759. 

3 La Presse Med., 1901, p. 145; and Eev. d'Obstet. et de Gyn., 1904, No. 8, p. 164; 
also C. R. Soc. de Biologie, 1900, lii., p. 1030 ; ibid., 1901, liii., pp. 106 and 285. 



THE MICROBIC THEORY OF CANCER 255 

The serum employed was obtained from the blood of asses and geese, 
that had previously undergone a series of inoculations with blastomycetic 
cultures. 

Foulerton * has made inoculation experiments in animals with various 
pathogenic yeasts. In most cases these caused death in from a few days 
to a few weeks. In many instances granulomatous swellings formed at 
the site of inoculation ; and from these the yeasts were again cultivated. 
He concludes that : " Considerably more evidence than is now available 
must be brought forward, before we can form any opinion as to whether 
Russell's fuchsin bodies etc., are merely parts of the cancer cells them- 
selves, or whether they are of the nature of animal or vegetable parasites." 
It is not improbable that some tumours, now classed as sarcomata, may 
really be due to yeast infection ; but, " as to the exact causation of carci- 
noma we are still absolutely ignorant." 

Klein, 2 having discovered a pathogenic yeast in some ordinary 
country milk, found that when inoculated subcutaneously into guinea- 
pigs, it produced tumour-like swellings at the seat of inoculation. When 
the animals were killed some weeks later, the tumours were found to be 
crowded with yeast-ceUs. Other guinea-pigs were inoculated with the 
juice of these tumours and with sub-cultures, with the result that similar 
tumours again formed, and death sometimes resulted. In the latter 
cases, yeast-cells were found in the blood. This yeast seemed to belong 
to the same group as the blastomycetes of Sanfelice. 

Gilchrist 3 has described a case of skin disease ("blastomycetic 
dermatitis ") in man, in which the lesion teemed with blastomycetes, 
wliich were seen multiplying by budding. He considers that most of 
the so-called parasites, in certain skin affections, are merely products 
of nuclear and protoplasmic changes of epithelial cells, and not organisms. 
Since formations of this kind are found in simple skin diseases, as well as 
in cancers, they can have no specific causal relation to malignancy. 
Clinically the above case resembled " scrofuloderma." 

Gilchrist and Stokes 4 have since reported another example of human 
blastomycetic infection. In this case the patient was a man, aged 
thirty-three, with a cutaneous disease like lupus vulgaris. It began 
eleven and one-half years previously, as a pustular pimple on the back 
of his left ear. Thence the morbid process spread slowly over the face, 
the older parts cicatrizing. A similar lesion formed, soon after the 
initial outbreak, on the back of his hand ; but this healed, on treatment 
with caustic, about four years after its first appearance. Six months 
later a third lesion appeared on the scrotum, which spread for a year, 
and then healed spontaneously. Other lesions formed on the left thigh, 
back of the neck etc., and likewise healed spontaneously after some 
time. There was no enlargement of the adjacent lymph-glands, and the 
patient's health remained good. There was no history of tubercle] or 
syphilis. 

1 Journal of Pathology and Bacteriology, May, 1899, p. 57 ; also ibid., 1900, vol. vi., p. 154. 

2 Transactions of the Pathological Society, London, 1901, vol. lii., p. 270. 

3 Johns Hopkins Hospital Reports, 1896, vol. i., p. 269. 

4 Journal of Experimental Medicine, January, 1898, vol. iii. ; also Butt. Johns Hopkins 
Hospital, July, 1896. 



256 THE NATURAL HISTORY OF CANCER 

Sections of the cutaneous lesions, on microscopical examination, 
showed numerous budding blastomycetes, in association with which were 
many almost typical tubercles. The organisms were mostly extra- 
cellular, comparatively few being included in the giant-cells. Pure 
cultures were obtained from the lesion, which grew well on potato and 
beer- wort agar. The cultures showed both budding forms and mycelium, 
although the latter was not met with in the lesion. A horse, a sheep, 
dogs and guinea-pigs were successfully inoculated, nodules forming 
which resembled tumours, especially in the lungs. Since the parasite 
did not ferment sugar, and produced mycelium in cultures, it might 
belong to the blastomycetes or o'idia. The authors suggest that all 
quasi-tuberculous lesions of the skin should be examined for similar 
organisms, which can easily be done by soaking unstained sections in 
liquor potassae, when the organisms may be recognized under the micro- 
scope as doubly contoured refractive bodies. 

A considerable number of somewhat similar cases have since been 
recorded, in some of which the lesions were very like those of ulcerated 
cutaneous cancer. 

Owens, Eisendrath, and Ready 1 have described an instance of this kind. 

Hyde, Hektoen, and Bevan 2 have reported the case of a man, aged 
fifty-six, with a peculiar form of skin disease caused by blastomycetes. It 
began four years previously, as a raised red tubercle which gradually 
extended ; until, when it had attained considerable size, it was removed 
by operation. A warty growth then appeared on his hand. A year later 
this was extirpated, and examined by Hektoen. Sections under the 
microscope showed blastomycetes ; and, in cultures, mycelium appeared. 
Rats and mice subcutaneously inoculated died in a few days ; and similar 
organisms were found in the lesions as in the inoculation sites. A striking 
feature of the histological sections was, the epidermoidal hyperplasia and 
its branching ingrowths. In the vicinity were numerous small aggrega- 
tions of leucocytes and miliary abscesses, and in these localities giant- 
cells were plentiful. 

The numerous publications on this subject, have been ably reviewed 
and summed up in Ricketts' 3 interesting monograph, to which the reader 
is referred for further details as to the cases etc. He noticed that, in 
several instances, the cutaneous lesions were " carcinomatoid " in their 
gross, and even to some extent in their minute structural features ; 
while still more cases simulated skin tuberculosis. Histologically the 
lesions comprised hyperplasia of the deeper layers of the epidermis, with 
ingrowing processes of the same, and infiltration of all the constituents 
of the cutis by leucocytes, with minute abscesses in the corium etc. The 
microbes producing these lesions comprised three types oidium-like 
(torula), blastomycetoid (saccharomycetes or yeasts), and hyphomycetoid 
(mould fungi), most of the organisms appertaining to the first-named 
group. 

In addition to these skin lesions, in several recorded cases, the malady 

1 " Pseudo-epithelioma with Blastomycetes," Annals of Surgery, 1899, vol. xxx., p. 545. 

2 British Journal of Dermatology, 1898, vol. ii., No. 129. 

3 Journal of Medical Research, February, 1902 ; and December, 1901, p. 377. 



THE MICROBIC THEORY OF CANCER 257 

presented in mankind as a generalized infection, with fatal issue in a few. 
Cultures were obtained from the pus, and from the diseased tissues. 
Attempts to produce the typical lesions in mankind, by inoculation with 
cultures, have so far failed most individuals being naturally immune ; 
animal inoculation has also generally been unsuccessful, but in a few 
cases tumour-like nodules formed, and oftener abscesses. 

Foulerton 1 has published the results of further study of this matter, 
comprising the bacteriological examination of several hundred human 
malignant tumours. In the course of this research, various types of 
microbes were cultivated from many of the tumours examined ; but, in 
not a single specimen, was a yeast found. Hence, he regards the presence 
of yeasts in such cultures as the result of contamination ab extra ; and, 
the cultures actually obtained, he considers as due to aerial contamina- 
tion, terminal infection, or invasion from an ulcerated surface. His 
general conclusions are as follows : A hypothetical cancer parasite does 
not in any way elucidate the pathology of cancer. So far as theoretical 
considerations go, the probabilities are against the theory of cancer being 
a parasitic disease. There is no evidence that any of the parasites which 
have been described as the cause of cancer, have any setiological relation 
to the disease. 

Nichols, 2 as the result of a thorough study of the subject, has inde- 
pendently arrived at very similar conclusions, which he formulates as 
follows : 

Certain blastomycetes can live and multiply in human and animal 
tissues, producing local lesions, and disseminating in distant parts, i.e., 
they are pathogenic. These lesions are never really cancerous. Blasto- 
mycetic infection is rare in humanity. Blastomycetes, as a rule, cause 
marked tissue proliferation, with but little infiltration by leucocytes, i.e., 
their toxic power is small. The morphology of the so-called " cancer 
bodies," is not identical with that of the blastomycetes. Blastomycetes 
are not constantly present in human malignant tumours. Even if blasto- 
mycetes do occur in human cancers, they are never found in such relation 
to the morbid formation, as to justify the belief that they are the cause 
of the disease. A general survey of the ascertained facts, reveals no 
evidence of any weight, that blastomycetes have anything to do with the 
causation of human cancers. 

Since Koch formulated his celebrated postulates, for determining the 
setiological relation of a parasite to a given morbid condition, an addi- 
tional test has been established by the study of agglutinative reactions. 
In this connexion, Malvey 3 has shown that the serum of animals inoculated 
with yeasts, has the power of agglutinating those yeasts. Tested in this 
way, the " cancer yeasts " fail to give any indications suggestive of casual 
relationship to cancer ; for, as Brauha 4 has proved, the serum of cancer 
patients when thus tested, does not give the agglutin reaction. 

Skchiwan, 5 recognizing the existence of blastomycetes in animal 

1 Practitioner, 1902, vol. Ixix., p. 213; and Middlesex Hospital Cancer Reports, 1902, 
vol.^i. 

2 Second Report of the Cancer Committee of Harvard Medical School, 1902, p. 80. 

3 Cent. f. Bakt., etc., 1901, Bd. xxix.. S. 688. 

4 Ibid., Ed. xxx., S. 945. 5 Ann. de I'Inst. Pasteur, 1899, t. xiii., p. 771. 

17 



258 THE NATURAL HISTORY OF CANCER 

bodies, has proceeded to study their fate under these circumstances. 
Working with Saccharomyces subcutaneus tumefaciens of Curtis, and 
other yeasts, he concluded that the destruction of pathogenic as well as 
of non-pathogenic blastomycetes, is effected by the digestive powers of 
leucocytes, which take up the living organisms and destroy them (phago- 
cytosis). Skchiwan claims to have seen yeasts multiply by budding 
within the phagocytes. He concludes that the destruction of yeasts 
within the body takes place, in accordance with the general laws of 
phagocytosis. The capsule, which sometimes forms round blasto- 
mycetes embedded in the tissues, he regards as a defensive arrangement 
by the organism against the further spread of the parasites. 

In concluding this section on the blastomycetes and their supposed 
> relation to tumour formation, attention ought to be called to De Backer's 1 
work in this direction. De Backer approached the subject from a totally 
different standpoint to that adopted, by any of those to whose work I 
have previously referred. He thought that by the introduction of blasto- 
mycetes into the body, an artificial phagocytosis might be set up, by 
which any pathogenic microbes that were present would be "Destroyed. 
Assuming that cancer was a germ disease, he proposed to treat it and 
other germ diseases such as tuberculosis, diphtheria, typhoid fever etc., 
by the injection of pure cultures of yeasts. 

It appears that the phagocytic properties of the saccharomycetes 
and some other organisms, were known to Bruhat and De Backer as far 
back as 1892. During microscopical examination of some wine that had 
gone wrong, Bruhat noticed that some of the cells of the ferment (Saccharo- 
myces pastorianus) had included in them other cells, viz., those of Bacillus 
aceti. The two observers then instituted a series of experiments for the 
elucidation of this phenomenon. They found that young cells of most 
kinds of saccharomyces, were very energetic phagocytes for all kinds 
of bacteria, englobing and digesting them. From this it seemed to 
follow, if Metchnikoff's theory of immunity were correct, that organisms 
of this kind, injected into the blood of animals infected with pathogenic 
microbes, would greatly assist the leucocytes in their phagocytic work, 
provided that they could exist in the blood and tissues of their host, 
without producing ill-effects. 

To test the practicability of this method, guinea-pigs and other 
animals were inoculated with the ordinary yeasts of commerce ; but, 
the results were not encouraging, for owing to the presence of impurities 
the yeasts often proved pathogenic, causing abscesses etc. Pure cultures 
of Saccharomyces cerevisice, injected with aseptic precautions, were there- 
fore substituted, and these proved innocuous. The animals were next 
injected with pure cultures, mixed with sterilized fermentable matter ; 
and experiments were made, which showed that under these circumstances 
fermentative changes occurred within the body of the animals experi- 
mented upon, which were none the worse for it. Animals infected with 
bacterial diseases, were next treated in the same way. Guinea-pigs 
infected with tuberculosis and diphtheria, recovered under this treatment. 

1 "De la Cancerose et de son Traitement par les Ferments purs." Clermont (Oise) ; 
also " The Ferment Treatment of Cancer and Tuberculosis," H. Manders, London, 1898. 



THE MICROBIC THEORY OF CANCER 259 

The plan was then tried on man. Bruhat, offering himself for experi- 
mentation, was injected in the flank. At the end of five hours a chill 
occurred, followed by sweating and symptoms of mild intoxication. At 
the end of three days the reaction had quite ceased, and no harm resulted. 
The infection caused leucocytosis. Phthisical patients were next inocu- 
lated, and it is claimed that, in early cases, the disease was nearly always 
arrested ; and most other cases improved, the main condition for success 
being that the cultures inoculated shall be absolutely pure. 

In the treatment of malignant tumours De Backer claims, with this 
method, to have achieved astonishing results : of sixty cases there were 
eighteen cures, lasting over some years ; and, in many others, the pro- 
gress of the disease was markedly retarded. 

Here mention may be made of the fact demonstrated by Pasteur, 
more than a quarter of a century ago, that the saccharomycetes can obtain 
every requisite for their growth in the human body, except that their 
main food, sugar, can be obtained only in small quantities. This 
deficiency explains the slow growth of these organisms in normal animal 
bodies, as compared with their rapid growth in sugar-containing media. 

To explain the curative effects of these injections in malignant tumours, 
De Backer makes use of this hint. He noticed that many of his guinea- 
pigs, which had lived together in full liberty, while subjected to a long 
course of pure yeast injections, got very fat and at the same time became 
sterile ; so that, even when occasionally impregnation did occur, the 
foetus failed to develop. He conceived that this sterility was due to 
diminished production of glycogenous material in the uterus etc., con- 
sequent on yeast injections. It is known that localities specially prone 
to cancer, such as the uterus, breast, liver, stomach etc., are normally 
rich in glycogen ; and, as Brault and others have shown, all malignant 
tumours are also remarkably rich in this material, which is said to be 
absent from granulomatous inflammatory new formations. Moreover, 
we know that the blood of cancer patients is also unusually rich in sugar- 
forming substances. 

With these points in view, De Backer concluded that blastomycetes 
artificially introduced into the body, by using up its glycogen for their 
own growth, might check the pathological increase of this substance ; 
and so starve the young cancer cells, by depriving them of their essential 
nutriment. Thus the whole tumour would shrink ; for, as Brault had 
shown, the rapidity of the increase of malignant tumours was directly 
proportional to the amount of glycogen they contained. 

In this connexion, it is interesting to note, that of late many instances 
of the association of malignant tumours with diabetes have been reported 
(Kappler, Boas, Kreutzmann, Tuffier, and others) ; and, most of those 
who have specially studied this subject, maintain that the diabetic state 
favours the development of malignant disease. 1 

It may be said to be established, as the outcome of these and other 
experiments, that injections of yeast produce leucopenia, which is rapidly 
followed by leucocytosis ; with consequent large increase in the antiseptic 
substances, normally present in the blood-serum. 

1 For some further remarks on this subject, vide Chapter XVI. 

172 



260 THE NATURAL HISTORY OF CANCER 

Mould-like Fungi. 

Even as far back as 1879, I became aware of the fact that mould-like 
fungi grow readily in human tumours. This was particularly impressed 
on my memory by a case that came under my notice in that year, in the 
clinic of Broca, at the Necker Hospital in Paris. 

The patient was a woman, aged fifty-eight, with a large, eroded, 
fungating, cauliflower-like tumour of the right breast. A lump had 
appeared in the breast, after her last confinement, nineteen years pre- 
viously : eight years later, this heretofore comparatively stationary lump 
began to enlarge, the overlying skin ulcerated, and the tumour soon 
afterwards fungated ; the protruding mass was then cut off, but it 
soon grew again ; and the present tumour was the gradual outcome of this 
recrudescence. On examination this tumour was firm and non-adherent 
to the chest wall ; the nipple was not retracted ; and there was no enlarge- 
ment of the adjacent lymph-glands. The diagnosis was fungating fibroma 
of the mamma. The breast with the tumour was removed. Histological 
examination showed that the real tumour growth consisted of fibro- 
cellular tissue, in which were embedded small cysts, lined by a single layer 
of cubical epithelium, evidently derived from the ducts of the mamma. 
The histological report, by Latteux, of which I still have a copy, says 
the appearances exclude the idea of sarcoma : " C'est, en somme, un 
fibrome en voie de developpement, tumeur essentiellement benigne." 

Now, the whole of the extensive surface of the fungating part of this 
tumour, was covered by a thick layer of coarsely mammillated granulation 
tissue ; which was pervaded throughout, to a considerable depth, by the 
mycelium and spores of a mould fungus, of which Latteux's report 
gives a good sketch although no trace of this parasite was noticeable 
to the naked eye. 

The fungus was, of course, regarded as a mere epiphyte ; for, at that 
time, no one thought of ascribing the origin of tumours to such parasites. 

In comparatively recent times, instances of spontaneously occurring 
granulomatous pseudo-plasms due to the mould-like fungi, have been 
met with in the skin (Schamberg, Ricketts, Delepine etc.), and in the 
gastric mucosa (Max Einhorn) ; and similar tumours have been artificially 
produced by injection of pure cultures of various mould-like organisms 
(Charrin and Le Play, Roth well etc.). 

An interesting case of this kind, which had been diagnosed after 
histological examination as " myeloid sarcoma," has lately been reported 
by Coley and Tracy. 1 

So far as I know, Bra 2 (" Le champignon parasite du cancer") was 
one of the first to ascribe the causation of cancer, to the presence of 
organisms of this kind. By culture methods, he isolated from malignant 
epithelial and connective-tissue tumours, of various parts of the body, 
as well as from the blood of the patients, a specific cancer microbe, which 
he regards as an " ascomyces." His cultures were made by insemination 
of portions of the tumours, and by inoculations from the blood of affected 

1 Journal of Medical Research, 1907, vol. xvi., Xo. 2. 

2 C. R. Acad.desSci., Paris, 1900, t. cxxxi., p. 1012; also LaPresse Med., 1899, vii., p. 87. 



THE MICROBIC THEORY OF CANCER 261 

persons. The medium used was cow's udder bouillon, and the culture 
appeared as a scum and a sediment, after from five to eight days' incuba- 
tion at 86 to 95 F. 

The organism was of spheroidal or cylindrical form, and multiplied 
chiefly by sporulation, mycelia being formed. In dogs and rabbits, inocu- 
lated subcutaneously with these cultures, tumour-like swellings were pro- 
duced, which histologically resembled malignant tumours epitheliomata 
and sarcomata. By inoculating a bitch in the mammary region, Bra 
claims thus to have produced typical mammary carcinoma. From these 
artificially produced tumours, pure cultures were made, which contained 
organisms just like those found in the original tumour. The inoculations 
into guinea-pigs proved inert. 

Curtis l of Lille, who repeated Bra's experiments, declares that after 
having taken precautions to eliminate extraneous organisms and other 
sources of error, neither cultures nor inoculation results could be obtained. 
He found that all tumours, even when not ulcerated and not contiguous 
to a free surface, nevertheless teemed with microbes ; while ulcerated 
tumours simply swarmed with innumerable kinds of microbic life. He 
concludes that human cancers are neither cultivable nor inoculable ; and 
that experiments hitherto published to the contrary, are due to errors 
of technique etc. 

Niessen, 2 while examining the blood of a woman with advanced 
uterine cancer, found in it an organism, which he believed to be the 
cause of the disease. In this blood a dark green mould developed, which 
was cultivable. It proved to be an unknown species of organism, inter- 
mediate between a mycete and a mould. It grew with great luxuriance 
in human blood, in sterile diabetic urine, and in water ; and the products 
of the cultures in these different media were themselves so diverse, that 
it was difficult to believe they were derived from the same source. This 
organism Niessen named Canceromyces or Cladosporum cancer ogenes. 

Braithwaite, 3 as the result of histological examination of sections of 
malignant tumours, found the morbid tissues pervaded by the spores 
and mycelia of a mould-like organism, which he regarded as the cause 
of the disease. Fungoid parasites were nearly always present in the 
specimens he examined ; and he claims to have discriminated eight or 
nine different kinds of them in various forms of cancer, each corresponding 
to a particular variety of malignant disease. Braithwaite has also found 
fungoid organisms in non- malignant growths (e.g., uterine myoma) ; 
hence, he conjectures that non-malignant tumours may also be of 
parasitic origin 



General Conclusions as to Blastomycetes etc. 

Amid the hubbub of conflicting statements as to the relation of 
blastomycetes and malignant tumours, we may, I think, discriminate 
the following propositions : 

1. Certain blastomycetes are pathogenic for man and animals, and 

1 Lancet, 1899, vol. i., p. 801. 

2 Cent. f. d. med. Wissenscliaften, Xr. 21, 1894. 3 Lancet, June 29, 1895. 



262 THE NATURAL HISTORY OF CANCER 

they may even cause in them lesions, which in their gross features some- 
what resemble malignant disease. Thus, instances of pseudo-sarcomatous 
tumours, due to the presence of organisms of this kind, have been reported 
in mankind by Curtis, Busse, Coley etc. ; while quasi-epitheliomatous 
lesions of similar origin, have been met with by Gilchrist, Owens, Hyde, 
Hektoen, and others. It also appears that certain oidia (Obici, Ricketts), 
aspergilli (Renon, Saxer, Boyce, Rothwell), bothryomycetes (Delore, 
Poncet), and probably other organisms, may originate similar morbid 
conditions. 

That tumour-like swelh'ngs, which are often confounded with sar- 
comata, may be caused by actinomycetic infection, is now generally 
admitted by pathologists. Moreover, tumours of this kind are not 
particularly rare, and they have been seen in almost every part of the 
body. As Wolff and Israel have shown, pure cultures of these organisms, 
injected into rabbits, give rise to tumour-like swellings. 

When carefully examined, these parasitic pseudo -plasms are found to 
differ markedly from true malignant tumours, both structurally and in 
their clinical features ; and they should evidently be classed with the 
infective granulomata. 

In consequence of these important discoveries, certain anomalous 
pseudo-malignant lesions, which have long puzzled pathologists and 
clinicians, may now be moved from the category of malignant neoplasms 
into that of the parasitic infections. 

2. So many pathologists have succeeded in obtaining pure cul- 
tures of blastomycetes from human malignant tumours, that I regard 
the liability of the latter to blastomycetic infection as having been 
proved, although not a few investigators have failed to get positive 
results. Considering the richness of these tumours in sugar-forming 
materials, which are so favourable to the growth of blastomycetes, it 
would indeed be strange if they were not more prone to this kind of 
infection than the normal tissues of the body. 

3. In their young and nascent condition, it has been repeatedly 
demonstrated, notwithstanding many assertions to the contrary, that 
non-ulcerated malignant tumours are quite free from blastomycetes. 

4. The repeated failures to produce malignant tumours in animals, 
by inoculation experiments with cultures of blastomycetes, prove that 
the latter cannot be the specific causative factor of malignant disease. 
The few instances in which it is alleged that malignant tumours have 
been thus caused (Sanfelice, Bra, Leopold etc.), are capable of being 
otherwise explained (blastomycetic or other granulomata, spontaneously 
arising malignant disease etc.) The ensemble of many experiments 
clearly shows, that yeast organisms etc., are incapable of causing the 
formation of true malignant neoplasms (epithelioma and sarcoma). 

The Question of Infection. 

In previous chapters, 1 I have already had occasion to refer to the 
subject of infection ; but, to complete the matter, some aspects of this 
important question still remain to be studied. 
1 Chapters IV. and VIII. 



THE MICROBIC THEORY OF CANCER 263 

In comparatively recent times, attempts have been made to utilize 
the irregularities invariably met with in the topographical distribution 
of cancer, as evidence of the infectious nature of the disease ; which, it 
is alleged, may manifest epidemic, endemic, and even pandemic char- 
acters. Hence, we now often hear of " cancer districts," " cancer houses," 
and even of " cancer rooms." 

Arnaudet * was the first, who formulated ideas of this kind. In 
certain remote rural districts in Normandy, he found that cancer was 
twice or thrice as prevalent as in Paris, where the disease is of great 
frequency ; thus, in the little hamlet of St. Sylvestre de Cormeilles, the 
cancer mortality for a period of eight years averaged no less than 
14-88 per cent, of the total deaths. He also adduced instances of cancers 
coexisting in various organs of persons living in certain houses or in 
their vicinity. Hence, he concluded that the locality where a cancer 
patient had lived was contaminated ; and he thought it probable that 
the contagion was spread chiefly through drinking polluted pond-water, 
which also contaminated the local cider, etc. Similar instances were 
soon afterwards advanced by Sorel, Guelliot, Fabre, Fiessinger, Webb, 
D'Arcy Power, Behla and others. 

Webb 2 reported the following remarkable group of cases : 

In. a village not far from his residence were two houses under one roof, 
with water-supply and drainage in common. Let us call them Nos. 1 
and 2. Twenty-six years ago a man aged twenty-eight, living in No. 1, 
died of cancer of the rectum. Mr. J. H. and his wife next occupied this 
house. His age was then sixty. Two years later he died of cancer of 
the stomach. His widow, who continued to live in the same house, died 
in it ten years later of cancer of the rectum. 

Prior to her death, Mrs. R., aged fifty, who lived in No. 2, was found 
to have cancer of the breast, which ended fatally eight months later. 

After the death of Mrs. J. H., No. 1 was occupied by three maiden 
ladies. Of these, Miss P. died four years ago, aged fifty-eight, of cancer 
of the uterus ; Miss F., who nursed her, died last winter, aged sixty-one, 
of cancer of the stomach ; the other sister was still alive and well. 

None of these persons were blood relatives ; and, in none of the 
families, was there a history of cancer in other relatives. 

In support of the infectious nature of the disease, it is alleged that the 
dwellers in certain houses, and even in certain rooms, may become affected 
with cancer, either simultaneously or successively, with undue frequency ; 
that instances of the disease attacking two persons living together (cancer 
d deux) are relatively frequent ; and that, in certain localities, so many 
cases may be met with as to constitute veritable epidemics. 

Fiessinger 3 has met with several examples of such outbreaks. 

Thus, in a small village, a woman died of cancer of the breast, and 
within a comparatively short space of time, two other women lodging 
in the house died of the same disease one of the rectum and the other 

1 Nortnandie Med., 1890, iv., p. 33; also L' Union Med., Ap. 25, 1889; Normandie 
31ed., Ap. 1 and Ap. 15, 1890; also Feb. 15, 1891. " Xouveaux faits k 1'appui de la 
nature infectieux du cancer." 

2 Birminghsim Medical JReview, 1892, vol. xxxii., p. 342; also ibid., 1894, vol. xxxvi., 
p. 209. 3 Jkvue de Mid., January, 1893. 



264 THE NATURAL HISTORY OF CANCER 

of the vulva ; and, after a certain time, two neighbours also died one 
of cancer of the stomach, and the other of sarcoma of the leg. 

He believes that these " epidemics " are particularly apt to occur on 
the banks of rivers, at the borders of woods etc., and he suggests that 
insects, which are plentiful in such places, are concerned in disseminating 
the disease, as well as contaminated fingers etc. 

Guelliot l of Reims has reported forty cases, in which malignant disease 
appeared to have been spread by contagion. He claims to have proved : 
(1) that malignant disease is unequally distributed in adjoining districts, 
in such a manner that neither heredity nor consanguinity will account 
for it ; (2) that there are real " cancer houses," the dwellers in which, in 
the absence of blood relationship, are nevertheless successively or simul- 
taneously attacked by malignant tumours ; (3) that cases of malignant 
disease attacking two persons living together are relatively frequent ; 
and (4) that of one hundred such cases, eighty-five were man and wife, 
and eight were medical practitioners, who had been engaged in the treat- 
ment of cases of malignant disease. According to Guelliot, these facts 
show that cancer is an infectious disease, which is transmitted directly 
or indirectly by contagion. It is alleged that cancer is prone to occur 
in damp, low - lying situations, in the vicinity of sluggish streams, 
in marshy areas, in localities prone to floods, in sewage-saturated regions, 
in places having a retentive subsoil, such as clay, in the vicinity of trees 
etc. ; and that this infection is spread by water, uncooked vegetables, 
insects, domestic animals etc. 

D'Arcy Power 2 claims to have demonstrated localized epidemics of 
cancer in certain districts, villages, houses, and " even in a single room "; 
but, beyond the bald narration of certain exceptional occurrences, which 
of themselves are by no means convincing, he has not even attempted to 
prove his thesis. 

Bosc, 3 having noticed the frequency of parasites and parasitic tumour- 
like swellings in fishes, believes that many outbreaks of cancerous disease 
are due to this cause. He thinks that gastro-intestinal cancer is often 
caused, by the bones of small fish wounding parts of the alimentary canal. 
External cancers, he maintains, are often due to infection carried by 
insects and various animals ; by contaminated fingers and polluted water ; 
and even by fleas, bugs, flies etc. 

In a previous chapter, 4 I have referred to Haviland's interesting 
researches, as to the influence of local geological and topographical con- 
figuration in the incidence of cancer ; and I have there explained my 
reasons for being unable to give them more than a certain limited accept- 
ance. 

In 1899, a committee appointed by the Birmingham Branch of the 
British Medical Association, 5 investigated the influence of locality on 
the incidence of malignant tumours, in parts of Warwickshire, Stafford* 

1 Oaz. des Hdpitaiix, 1892, No. 139. 

2 British Medical Journal, 1894, vol. i., pp. 1240 and 1302; ibid., April 27, 1895; 
also Edinburgh MedicalJournal, 1902, vol. xii., p. 39. 

3 "Le Cancer," Paris, 1898. * Chapter IV. 

6 British Medical Journal, 1899, vol. i., p. 812 ; also Birmingham Medical Bevieic, 
May, June, and July. 1900. 



THE MICROBIC THEORY OF CANCER 265 

shire, Shropshire and Worcestershire. They concluded, that there were 
districts in which this disease occurs with frequency much above the 
average, side by side with other districts in which it is rare. The high- 
mortality districts were usually poorly drained, flat, low-lying or border- 
ing on streams ; whereas the low-mortality districts, were high, dry, and 
well drained. They believe that there is a direct connexion between the 
presence of subsoil water within a certain distance of the surface, and 
the prevalence of malignant disease. 

They also found that second and third cases of cancer occur in par- 
ticular houses, more frequently than can be accounted for by coinci- 
dence ; that particular groups of houses, perhaps in the same street, may 
be similarly affected ; and they suggest that this association implies 
contaminated soil. Old houses also appeared to furnish a higher pro- 
portion of cancer cases, than new ones. 

Scott, 1 after having studied the prevalence of cancer in the Chelmsford 
and Maldon districts of Essex, concluded that whatever truth may underlie 
Haviland's theory, it is insufficient to explain the distribution of cancer 
in these parts. Essex is a flat, marshy county, with a clayey subsoil, and 
it used to be the home of malaria ; yet the cancer death-rate for the 
county is by no means high, being below the average for England as a 
whole. Although the unions of Chelmsford and Maldon, contain an 
excessive proportion of marshy land and estuary (" saltings ") ; yet, their 
cancer death-rate, is less than that of the whole county. Those parts of 
the two unions which include the greatest extent of muddy foreshore, 
creek, and " saltings," have a smaller cancer mortality, than that of the 
whole of the two unions taken together. The disease was found not to be 
specially prevalent, in places situated on the banks of the fresh-water 
rivers. In these parts of Essex, therefore, the cancer mortality bears no 
evident relation to the variations in the physical features of the country. 

Noel 2 finds that in " cancer districts " certain contagious, tumour- 
like growths are often seen on the trees, which have a certain resemblance 
to malignant tumours. He thinks that between these " arboreal cancers " 
and human malignant disease, there is some aetiological connexion, for 
the latter are of frequent occurrence in persons living surrounded by or 
near woods. Cancer of the lip, he says, never originates in Lyons ; 
but all those having the disease in that city, are found to have 
contracted it in the country. Noel considers it as proved that insects, 
especially certain wasps, have a special predilection for " arboreal 
cancers " ; and that they carry the infection not only from tree to tree, 
but also disseminate, it (through orchards etc.) in human foods. He 
maintains that human beings may thus be infected ; when the contagion 
enters by the mouth, gastro -intestinal lesions result, while external parts 
are attacked through contact infection. 

Behla 3 believes that cancer is a parasitic disease, which may be 
propagated like malaria ; and both maladies have, he thinks, some relation 

1 British Medical Journal, 1900, vol. ii., p. 420. 

2 " Sur la topographic et la contagion du cancer," Rev. des Mai. Cancereuses, Paris, 
1896-1897, ii., pp. 137 and 201 ; also These de Paris, 1897. 

3 Cent. f. Bakt., etc., 1898, Bd. xxiv., pp. 780, 829, 875, and 919 ; also Zeits. f. Hygiene, 
1899, Bd. xxxii., p. 123, etc. 



266 THE NATURAL HISTORY OF CANCER 

to damp, marshy conditions of soil. But differences in the soil, in the 
well-water, or in the atmospheric conditions, cannot account for such 
diversities in the incidence of the disease, as he has noted in different 
sections of the small agricultural town of Luckau ; thus, only the food 
remains. The inhabitants of the suburb in which cancer is so prevalent, 
are mainly small farmers and nursery-men, who eat large quantities of 
the uncooked vegetables, which they raise cabbages, radishes, water- 
cress, lettuces etc. Behla then points out, that these plants are liable 
to tumour-like diseases of parasitic origin, such as that caused in cabbages 
by Plasmodiophora brassicce. He has found drinking-water and vegetables 
teeming with these parasites, which he maintains are the infective agents 
of human cancer. The great frequency of gastro-intestinal cancer, 
points to the food as the chief means by which the contagion enters the 
body. 

The domestic animals such as dogs and cats as well as the rats and 
mice of Luckau, are prone to cancerous tumours ; and, Behla thinks that 
these animals may also be a source of contagion, by which the malady is 
communicated to mankind. He also claims to have proved that cancer 
clings to certain streets, houses, or groups of buildings, irrespective of 
their size and age. 

Behla has made special study of the house incidence of all cancer 
deaths in Luckau which comprises a stationary population of 5,000 for 
a period of twenty-two and a half years. During this period, about 1 in 
25 of the total deaths for the whole town were due to cancer, which is 
not a very high ratio. 

The central part of Luckau, which is low-lying and surrounded by 
ditches, comprising 3,000 inhabitants, furnished 65 cancer deaths. Of 
its 415 houses, in 33 there had been a single cancer death ; in 10, two 
such deaths ; and in 4, three cancer deaths. 

Its eastern suburb Kalau, which is also low-lying and marshy, being 
intersected by irrigation channels for market-gardening, comprising 
1,000 inhabitants, furnished 73 cancer deaths, or 1 in 9 of its total mor- 
tality. Of its 127 houses, in 45 there had been a single cancer death ; in 9, 
two cancer deaths ; in 2, three such deaths ; and in 1, four deaths. The 
cancer mortality of this suburb was fourfold that of the central part of 
Luckau. Of the 40 houses, comprising its main street, only 5 were 
without at least one cancer death ; and 56 of the total 73 cancer deaths, 
occurred in the houses of this street. 

In curious contrast with the foregoing, the high-lying and dry suburb 
of Sando, comprising 1,000 inhabitants, had not, a single death from 
cancer during the whole twenty-two and a half years. 

In estimating the value of these data it must be borne in mind, that 
no information is given as to the social condition, age and sex distribution 
of the contrasted populations, which alone might suffice to explain much 
of these diversities, judging by the experience gained as to the cancer 
mortality of such places as Hampstead, Clifton and Bath, to which I have 
previously referred ; moreover, the same reticence is manifest with 
regard to hospital accommodation, heredity, and the method of 
registration. It is not stated what proportion of those attacked with 



THE MICROBIC THEORY OF CANCER 267 

cancer, in each of the respective parts of the town, were treated and died 
elsewhere than at home. Then, again, it should be noted, that although 
the investigation comprised a series of years ; yet, owing to the small- 
ness of the community, the massif of the totals is far too small to 
enable reliable averages to be deduced therefrom. Hence, as evidence 
of infection, these much-paraded data have per se, but little scientific 
weight. 

From study of the cancer incidence in the Nuneaton and Stratford-on- 
Avon districts, E. N. Nason x concludes, that cases of cancer tend to group 
themselves chiefly in the vicinity of sluggish streams, and where the 
subsoil is indifferently drained, sewage-polluted etc. 

Lloyd Jones 2 has worked out the local distribution of malignant 
disease in Cambridge and its vicinity, during a period of nineteen years. 
He concluded as follows : (1) that some parts of the town are compara- 
tively free from the disease, while other parts, often contiguous, suffer 
severely ; (2) that elevated sites are less liable than low-lying ones ; 
(3) that the chalk subsoil is the freest from the disease ; (4) that proximity 
to the river is not always attended by a high cancer death-rate, although 
damp sites favour the disease ; (5) that proximity to trees, especially large 
ones, in some way favours the prevalence of cancer ; (6) that decaying 
vegetation, filth, collections of manure etc., are often found in cancer 
districts. 

Mason 3 has in like manner examined the problem of cancer distribu- 
tion, for the Leamington district of Warwickshire. He believes, whatever 
the ultimate cause of the disease may be, that it will be found to be 
associated with a sewage-contaminated subsoil ; that end houses of rows, 
corner houses of streets, and houses on either side of court-entries are 
often " cancer houses," owing to drain leakages and consequent sewage 
contamination being most frequent at those spots ; that old houses are 
more dangerous than modern ones for the same reason ; and that houses 
built on porous subsoil (sandstone, gravel etc.), are more prone to favour 
the development of cancer than those built on clay. 

Gifford Nash, 4 from the study of the distribution of cancer in North 
Bedfordshire, has arrived at the following conclusions : 

1. That the occurrence of cancer in that district, is a little above the 
average for England and Wales. 

2. That cancer appears to be less common in the urban, than in the 
rural districts. 

3. That the liability of the disease to attack the alimentary system is 
very great. 

4. That the percentage of cases at an elevation of 300 feet, is con- 
siderably greater than under 150 feet ; and also greater than that of the 
villages adjacent to the river Ouse. Hence proximity to the river, low 
elevation, liability to floods etc., does not increase the tendency to cancer. 

5. That the nature of the soil appears to have very little influence on 
the occurrence of cancer. 

1 British Medical Journal, 1898, vol. i., p. 679. 

2 Ibid., 1899, vol. i., p. 813. 3 Ibid., 1902, vol. i., p. 139. 

4 "Cancer, with special reference to its distribution in North Bedfordshire," 1903. 



268 THE NATURAL HISTORY QF CANCER 

6. That the large number of instances in which two or more cases 
occurred in the same house, or. in persons intimately associated, points to 
the disease being infectious. 

7. That infection, if it exists, is a very slow one, the usual interval 
between two cases in the same house and family, being about two years ; 
and the liability to infection increases with age, very few cases occurring 
under forty years. 

Symons l has made a careful inquiry as to the relation of cancer to 
the dwelling-house, as met with in Bath, a town of about 50,000 inhabi- 
tants, which has a high and progressive cancer mortality, with a low and 
diminishing tubercle death-rate. Its population, of whom two-thirds 
are females, has been stationary for the last half-century. This excess 
of females is largely due to the number of young women, employed as 
domestic servants etc. The population of Bath also comprises an 
unusually high proportion of middle-aged and elderly persons, especially 
females ; and comparatively few children under five years old. Another 
of its peculiarities is the well-to-do-ism of its inhabitants, the proportion 
of persons of " independent means " residing there," exceeding that of any 
other town in England. Its general health and sanitary conditions are 
good, typhoid fever and infectious diseases are rare, its general and 
tuberculous death-rates are low, and in all these respects progressive 
improvement is noticeable ; yet withal, its cancer mortality is very high, 
and for the last half-century it has been steadily increasing, until, at the 
present time, its corrected death-rate from this cause is 50 per cent, in 
excess of the average for the vicinity. 

This city is situated in a deep valley in the midst of hilly country 
which is traversed by a sluggish, sewage-contaminated river, prone to 
flood the adjacent lands ; it has a dense surface soil, overlying lias and 
oolite, which is permeated by numerous ground springs, the water being 
very hard. The town comprises many hills, and is surrounded and some- 
what shut in by them ; so that, although most of the houses lie in the 
hollow, many are built on the slopes of the hills, and most of the best 
residential houses enjoy quite elevated sites. 

In order to get at the facts, as to the precise local distribution of 
malignant disease in the town, Symons located houses, 1,212 in number, 
in which 1,319 deaths from this cause had occurred during a period of 
thirty-two years (1866-1897), among 8,507 houses. Of the houses in 
which these deaths occurred, the great majority, viz., 1,111, had only a 
single fatality in each house ; in 95 houses there had been 2 fatal cases ; 
and there were 6 houses in which 3 cancer deaths had occurred. These 
numbers were so little in excess of those that the usual mathematical 
method of calculating probabilities indicated, that Symons concluded 
neither the elevation, nor the aspect, nor the class of house, had any 
constant relation to the incidence of the disease ; and thus it was proved, 
so far as Bath is concerned, that there are no " cancer houses " there. 

Applying this method to the data for Cambridge, as compiled by 
Lloyd Jones who found that in nineteen years, among 5,685 houses, 
438 had harboured persons who had died of cancer, of which only 7 houses 
1 Public Health, December, 1898. 



THE MICROBIC THEORY OF CANCER 269 

had double cases and 3 triple ones Symons showed that this proportion 
of multiple fatalities was actually less, than that indicated by the calcu- 
lated probabilities ; so that in Cambridge, as in Bath, there were shown 
to be no " cancer houses." 

Hence Symons concludes, that there is no scientific basis for the 
doctrine of " cancer houses." 



General Conclusions as to Infection. 

As I have previously indicated, no evidence in favour of infection is 
forthcoming from any of the large hospitals, in which numerous cancer 
patients are constantly under treatment ; nor from those who are, in 
these institutions, constantly in close contact with, their inmates. 

It accords with this, that we never hear of " cancer epidemics " 
arising in the overcrowded parts of our great cities, where the density of 
population is at its maximum, and where sanitation is least regarded ; 
but, it is rather from remote, sparsely populated, rural districts, that all 
the instances of this kind have come. 

If cancer is an infectious disease, how is it that so few cases occur 
until after middle life ; whereas, in other infectious diseases, it is the 
young who are specially predisposed ? 

It appears to me, for reasons I have previously set forth, that variations 
in the incidence of cancer mortality, can be far more satisfactorily ex- 
plained, as the outcome of divergent conditions of existence, rather than 
as the result of infection. 

Indeed, it is remarkable that a high local cancer mortality, nearly 
always coincides with and is indicative of, healthy surroundings ; as is 
evidenced by the fact that there, the density of population is least, the 
tubercle mortality lowest, the average duration of life longest, the 
infantile and general mortality lowest, while infectious diseases are at a 
minimum : in short, among the wealthy and well-to-do, where the 
standard of health is at its best and life is easiest, there the cancer 
mortality is highest. 

Of this in London, Hampstead is a striking example ; in Bristol, 
Clifton ; and in Bath, as we have seen, it is the same. 

On the other hand, where sanitary conditions are least regarded, 
where the struggle for existence is hardest, the density of population 
greatest, and infectious diseases are most prevalent ; that is to say, among 
the workers of our large towns, there the cancer mortality is lowest. 

It accords with the foregoing, that malignant tumours are of great 
rarity in early life ; and, at this period, the epithelial form of the malady 
is practically unknown : in all these respects malignant tumours differ 
from infectious maladies in general. 

As against these weighty considerations, the curious medley of chaotic 
and conflicting statements, advanced by the advocates of infection in 
support of their thesis, seem to me to be of little worth. We need not 
seriously entertain these fairy tales, when their great progenitor the 
hypothetical microbe of cancer has been discovered. 



CHAPTER XI 

INFLAMMATION, TRAUMA, AND OTHER EXTRINSIC FACTORS 
Inflammation and Tumour Formation. 

THE leading pathologists of the nineteenth century were more profoundly 
divided, as to the essential relations of inflammation and tumour forma- 
tion, than on any other subject of the first importance in the whole 
range of pathology ; but, at the time, not much was said about it. These 
divergences, after having long lain comparatively dormant, have now 
under the stimulus of modern research flamed up again, in such a manner, 
that they cannot any longer be ignored. 

In a previous chapter, 1 I had occasion to refer to the peculiar 
position taken up by Virchow in this matter ; how that he, so to speak, 
ran with the Broussaisian hare, and hunted with the Miillerian hounds, 
as if the processes of inflammation and growth were identical ; whereas, 
as I shall now proceed to show, they are in every respect fundamentally 
different and distinct. It is noticeable, moreover, that Virchow's 
neoplastic pathogeny 2 is throughout dominated by the Broussaisian con- 
ception, that tumours are but forms of inflammation ; whereas the 
Miillerian doctrine, that tumours are due to abnormal growth, is used 
merely as a subsidiary hypothesis, to make good the more obvious short- 
comings and defects in the dominant hypothesis. It is Virchow's 
neoplastic pathogeny, thus vitiated ab initio by fundamental misconcep- 
tion, that the microbists have revived in recent times, accentuating its 
errors, with such results as I have set forth in the preceding chapter. 

The leading British exponent of the Broussaisian doctrine of tumour 
formation is Jonathan Hutchinson, 3 who has formulated his views as 
follows : " The propositions in reference to cancer, which I am chiefly 
concerned to maintain, are : First, that it is a modification of chronic 
inflammation, and that the same laws which are applicable to the one 
are, for the most part, applicable to the other. Second, that it is under 
the influence of inherited tendency and of senility, that processes inflam- 
matory in their outset tend to pass into those of cancer. Third, that 
cancerous processes are in their initiation local, and that the disease 
becomes constitutional by infection, by elements derived from the 
primary growth." 

Among those who combated the fallacies of Virchow's tumour doc- 
trine were Billroth and Cohnheim, both of whom, like J. Miiller, rejected 

1 Chapter VII. 

2 Die krankhaften Geschwulste, Bd. i. 

3 Archives of Surgery, October, 1890, p. 138. 

270 



INFLAMMATION, TRAUMA, AND OTHER FACTORS 271 

the inflammation theory. " A tumour," says Billroth, 1 " is a neoplasm 
that has not started from the same causes as excite inflammation ; but 
from others that are unknown, or but vaguely suspected." 

I think I have already made it sufficiently plain both in tin's and in 
other chapters, that my views on this important matter are entirely in 
accord with those of Miiller, Billroth and Cohnheim ; indeed, I believe 
that the Broussaisian doctrine of tumour formation, is mainly responsible 
for the comparatively small progress that has been made, during the last 
half-century, in tumour pathogeny this misconception having given a 
wrong bent to the direction of tumour research. 

For, since inflammation is the outcome solely of extrinsic causes, 
whereas the causes winch determine tumour growth are mainly intrinsic, 
it is obvious that of these divergent and incompatible ways, only one 
can be right. In order to make this antithesis quite clear, it is necessary 
to state what is meant by this conventional term " inflammation "; 
which is used as a cloak for a complex of diverse processes, as to which 
there is to-day even less agreement among pathologists than formerly, 
when there never was unanimity. 

The old conception of ' ; inflammation," which summed up the mixed 
processes connoted by the term, as the aggregate of its cardinal symptoms 
rubor, dolor, color, and tumor, to which may be added pyrexia, is as 
true now as it was in the time of Celsus ; because it is a mere description 
of externals, and does not concern itself with the underlying processes. 

The most important of these processes undoubtedly is microbic 
infection ab extra ; for, in the modern sense, there can be no inflamma- 
tion without microbes. In accordance with this, we see that extensive 
injuries are repaired without inflammation when microbes are excluded, 
as in simple fractures ; whereas, when this is not effected, the most 
violent inflammatory reaction ensues, as in compound fractures. Thus, 
the definition of inflammation, as " the succession of changes which 
occurs in a living tissue when it is injured," is altogether inadequate. 
The changes which take place in damaged structures, without the con- 
currence of microbes, by which restitutio ad integrum is effected, are -an 
outcome of the reparative process ; and have nothing to do with inflam- 
mation properly so called, although they are often improperly included 
within the scope of this term. Hence, we must also reject Grawitz' 
definition of inflammation, as " the reaction of irritated and damaged 
tissues which still retain their vitality." 

" Inflammation " being the term originally applied to certain appear- 
ances met with in mankind, and thence extended to similar appearances 
in the higher animals, which are the outcome of changes concentring in 
the lymph- vascular system, it follows that inflammation in this sense, 
can only occur in organisms and tissues possessing such a system, and 
capable of reacting to foreign microbes in this particular way. In short, 
inflammation is, as Cohnheim says, a particular kind of disturbance of 
the circulation. Hence, non-vascular tissues, and organisms in which 
the lymph- vascular system is not evolved (as in the lower forms of animal 
life and in all vegetable organisms), are incapable of " inflammation." > 
1 " Surgical Pathology," lecture xliv. 



272 THE NATURAL HISTORY OF CANCER 

" No inflammation without bloodvessels," is quite as much a truism, as 
" no inflammation without microbes "; and, in both of these fundamentally 
important respects, there is complete antithesis between growth and 
inflammation for the inception of growth is as independent of microbes, 
as it is of bloodvessels and nerves. 

Lately the tendency has manifested itself, chiefly as the outcome of 
Metchnikoff's teaching, to identify " inflammation " with phagocytosis, 
and even with " chemiotaxis "; but this would be to substitute new 
names for an old process in defiance of historical tradition, which in the 
matter of names is the paramount authority. 

Nothing has done more to obscure the fundamental antithesis between 
inflammation and tumour growth, than the failure of pathologists to 
discriminate between the phlogistic and the reparative processes, both 
of these perfectly distinct reactions being commonly included under the 
term " inflammation." 

This is specially noticeable in the condition called " chronic inflamma- 
tion," which in my opinion is not inflammation at all ; but an abnormality 
of growth, the outcome of imperfectly co-ordinated reparative efforts. 
Hence, it would be well if the term " chronic inflammation " were alto- 
gether abolished from modern pathology, as being essentially mis- 
leading. 

This confusion between " chronic inflammation " and the overgrowth 
marking imperfect repair, is the fundamental misconception which under- 
lies and vitiates ab initio the Broussaisian doctrine of tumour formation, 
the fallaciousness of which I have now sufficiently laid bare. 



Precancerous Conditions. 

It is an ancient belief, that cancer usually starts in a part of the 
body, which has undergone antecedent " inflammation," or some other 
departure from the normal ; rather than in a part quite free from any 
such aberration. 

As I have indicated in a previous chapter, 1 the proneness to originate 
cancer manifested by such pre-natal blemishes as " rests," moles, nsevi, 
and other developmental irregularities, shows that there is such a thing 
as congenital local predisposition to the disease ; and in this respect 
there is thus some warrant for the ancient belief. 

Moreover, I am persuaded that well-ascertained facts indicate, that 
repeated irritations of long duration and moderate intensity are, in a 
certain proportion of cases, the precursors of malignant disease. Further, 
I am convinced that parts thus chronically irritated, may thereby be 
rendered more apt to take on neoplastic action, than they otherwise 
would have been. In short, there is such a thing as acquired local pre- 
disposition to cancer. Thus may we account for the relative frequency, 
with which certain cutaneous cancers are met with in chimney-sweeps, 
and other workers in irritant substances, such as tar, paraffin etc. Here 
also belong the various " eczema cancers," " lupus cancers," " scar 
cancers," "x-ray cancers" etc. 

1 Chapter VII. 



INFLAM:\IATION, TRAUMA, AND OTHER FACTORS 273 

The Broussaisians, however, are not satisfied to stop here ; for, from 
such considerations as the foregoing, they draw the unwarrantable con- 
clusion ; that chronic inflammatory lesions are the necessary antecedents 
of cancer. It is against this doctrine that I protest ; and I will now 
proceed to show its erroneousness. 

The only evidence of any scientific value hitherto adduced in favour 
of the Broussaisian doctrine of cancer causation, is to be found in Volk- 
mann's * well-known analysis of 223 cases of primary cutaneous cancer 
of the extremities. In this connexion, it must be borne in mind, that 
although the extremities suffer more from all kinds of traumata, scars, 
burns, chronic ulcers etc., than any other parts of the body, they never- 
theless very seldom originate cancer. Of 7,297 consecutive primary 
cancers analysed by me, only 99, or 1-3 per cent., originated from the 
extremities ; and of these, 72 started from the lower and 27 from the 
upper. 

Xow, Volkmann found that in no less than 88 per cent, of his cases, 
the cancerous disease had originated in connexion with some pre-existing 
lesion of the part ; in only 12 per cent, did it appear to have sprung up 
spontaneously. If the state of things revealed by this analysis, were 
really representative of the ordinary mode of development of cancer, 
these data would be strong evidence in favour of the influence of 
irritation. But I maintain that it is not so. The cases analysed 
by Volkmann were not consecutive cases, but most of them had 
been recorded at various times by different observers, with the special 
object of showing the association between cancer and pre-existing 
local disease, as to the occasional occurrence of which there is no 
doubt. 

The fallacy of accepting these data, as typical of what takes place in 
the ordinary development of cutaneous cancer, is well seen by comparing 
Volkmann's results with the following analysis of 40 consecutively 
occurring cases of primary cutaneous cancer recorded by myself, 2 in which 
special attention was directed to the question of pre-existing disease of 
the part. Of these 40 cases, only 1 1, or 27-5 per cent., were associated with 
pre-existing lesions viz., old scars in 4 cases, congenital lesions in 2 ; 
suppurating sebaceous cyst, soot wart, wart of eighteen years' duration, 
recent wound, and chronic sinus, each in 1 case. In other words, the 
most careful examination, directed expressly to this end, failed to reveal 
the existence of any obvious pre-existing local disease, in 72 per cent. 
of all cases. In like manner, of 669 tumours analysed ad hoc by Rappok, 3 
32 per cent, started from some pre-existing lesion ; and, in 68 per cent., ' 
nothing of the kind was noticeable. 

By careful inquiries as to the association of the onset of cancer with 
pre-existing local disease, in other parts of the body, I have ascertained 
that, for these localities also, the foregoing conclusions are equally 
valid. 

1 Samml. klin. Vortrdge, 1889, Nos. 334 and 335. 

2 Middlesex Hospital Surgical Reports, 1882 to 1889. 
* Deutsche Zeits. f. Chir., Bd. xxx., S. 465. 



18 



274 THE NATURAL HISTORY OF CANCER 



In the Female Breast. 

Thus, with regard to the female breast, it is often asserted that cancers 
of this part, are due to antecedent attacks of inflammation or abscess, 
yet no conclusive evidence of this has ever been adduced. Equally 
destitute of support is the constantly reiterated assertion, that the latter 
lesions are of more frequent occurrence in the cancerous, than in the 
non-cancerous. 

The following facts are conclusive in this respect. 

Winckel l has estimated that after 1,000 consecutive accouchements, 
mastitis developed in 6 per cent. This, of course, refers only to its 
frequency after single deliveries in a succession of women ; and not to 
the frequency of its occurrence, in regard to the total pregnancies of 
each woman, during her entire puerperal life. To obtain the latter 
datum, Winckel's percentage must be multiplied by 4-6, this being the 
average number of accouchements of each married woman. Reckoned 
in this way, it will be found that 27 6 per cent, of all fertile married 
women have suffered, at some period or other of their puerperal life, 
from inflammatory disease of the breast. In order to ascertain what 
proportion of mammary-cancer patients suffer from similar affections, I 
made special inquiries on this subject in 137 cases. Of these, 24, or 
17-5 per cent., gave a history of some previous disease of the breast 
abscess in 15, sore nipple in 8, and inflammation in 1 ; and in 6 of these 
cases the nipples were congenitally malformed. 

The above facts prove, that cancer patients are less prone to inflam- 
matory diseases of the breast, than the non-cancerous. 

Hence, the only basis for this alleged causation is, that in a certain 
proportion of cancer cases, inflammatory lesions have pre-existed. 
Moreover, against the assumed setiological importance of previous inflam- 
matory disease is the fact, that in most of the cases, the interval between 
the antecedent disease, and the subsequent outbreak of cancer, extended 
over many years ; and, during this period, the breast appeared to be 
free from any lesion. Of like import is the fact, that cancer of the 
breast is relatively almost as frequent in the single and sterile as in the 
married, although the former are much less prone to inflammatory 
affections of the breast than the latter. 

On a priori grounds, no inflammatory lesion seems more likely to be 
the precursor of cancer, than chronic mastitis ; and; since this disease 
gives rise to circumscribed induration, its presence can hardly be over- 
looked. 

Yet how rarely does mammary cancer ever appear to start in con- 
nexion with such indurations ? I have met with this conjunction only 
twice, in 137 cases ; 2 hence it seems to me improbable that chronic 
mastitis plays an important part in the genesis of mammary cancer. 

1 Path. u. Therap. des Wochenb., 1878. 

2 According to Gross, cancer of the breast appeared to develop out of chronic inflam- 
matory induration in 49 out of 907 cases, or in 5'4 per cent. (International Journal of 
Medical Science, March, 1888, p. 222). 



INFLAMMATION, TRAUMA, AND OTHER FACTORS 275 



In the Uterus. 

Similarly, with regard to uterine cancer, it is alleged by Emmet and 
his followers, that the disease is almost invariably caused by child- 
bearing, lacerations, " endometritis," or some of the other maladies 
incidental to the married state ; while others attach great importance 
to catamenial derangements, the abuse of venereal pleasures, syphilis 
and gonorrhoea. 

As I have previously mentioned, cancer is a disease of persons whose 
previous life has been healthy, and whose nutritive vigour seems to promise 
long life. It accords with this, that the natural functions of cancer 
patients are almost invariably performed with ease and regularity. Thus, 
in women with uterine cancer, the normality of the catamenial function 
is seldom disturbed ; and, that it is established earlier and ceases later 
than in the generality of women, is an indication of vigorous sexual 
health. 

Just so is it with regard to marriage, for a much greater proportion 
of uterine-cancer patients have been married, than of the female popula- 
tion of corresponding age. 

Of 156 women with uterine cancer, under my observation, 146 (93-2 
per cent.) had been married, and only 10 (6-8 per cent.) were single ; 
similarly, of 168 cases tabulated by West and Duncan, only 3 were single ; 
thus, of these 344 uterine-cancer patients, 311 had been married, or 
96 per cent. ; and only 13 were single, or 4 per cent. In the general 
population only 79 per cent, of women over 24 ever marry. 

Of similar import is the great fertility of these cancer patients. 

Of 143 uterine-cancer patients under my observation, only 6 were 
barren (4-2 per cent.) ; of 528 patients under treatment at the Berlin 
Charite Hospital (1883-1893) 28 were barren (5-3 per cent.) : thus of these 
671 patients 34 were barren, or 5 per cent. Among married women in 
the general community, the amount of sterility is much more than this ; 
it has been estimated by Simpson at 11-6 per cent. 

The 137 fruitful women in my list, averaged 5-6 children and 0-9 mis- 
carriage each the maximum progeny being 13 children and 4 mis- 
carriages (of which there were 2 instances). 

With regard to one-child sterility, there were 10 instances of it, or 
1 in 13-7 ; which is almost identical with the ratio found by Ansell to 
prevail among fertile married women of the general population. 

To sum up, 143 married uterine-cancer patients had between them 
767 children and 123 miscarriages, the average being 5-3 children and 
0-8 miscarriage each. 

This amount of fertility exceeds that prevalent in the general com- 
munity, which averages about 4-6 children and 1 miscarriage per mar- 
riage ; when allowance has been made for the fact that a considerable 
proportion of uterine cancer patients die, before the completion of their 
reproductive life, it is obvious that their fecundity is even higher than 
from the foregoing figures it appears to be. 

The mean age at first marriage (in 63 cases) was 21-6 years ; and the 

182 



276 THE NATURAL HISTORY OF CANCER 

mean age at which child-bearing commenced (in 100 cases) was 21-8 
years ; both of these averages are considerably earlier than the corre- 
sponding figures for married women of the general community ; and they 
furnish another indication of the reproductive energy of these patients. 

It will be gathered from what has been stated, that uterine cancer is 
of more frequent occurrence in the married, and in those who have 
borne children, than in the single and sterile. Must we infer from this, 
that frequent parturition favours the development of the disease ? 
Certainly no such inference is warranted ; for, as the following data 
show, female cancer patients in general, manifest a similar high degree 
of fertility. 

Thus, 15 women with cancer of the rectum, averaged 6-3 children, 
and 0-7 miscarriage each ; 98 breast-cancer patients averaged 3-4 children 
and 1-1 miscarriages each ; 6 women with ovarian cancer, averaged 8-2 
children each ; 7 rodent-ulcer patients averaged 6-8 children and 2 mis- 
carriages each ; and 9 women with cancer of the tongue averaged 4 
children and 1 miscarriage each. 

It is evident, therefore, that the high degree of procreative capacity, 
manifested by these females, is merely one of the consequences of that 
exuberant general health and nutritive vigour ; which, as I have previously 
mentioned, is a peculiarity of cancer patients. 

It may be inferred, from the fact that 10 of the 156 uterine-cancer 
patients of my list, were unmarried, and all save one childless, that 
virginity is no safeguard against the disease ; and, if this evidence as to 
virginity be deemed insufficient, reference may be made to many pub- 
lished cases in which the presence of uterine cancer has been demon- 
strated, in women who presented all the anatomical signs of virginity. 

I have ascertained that in the great majority of uterine-cancer cases, 
the disease does not begin, until many years after the final cessation of 
child-bearing. Of 32 prolific women thus affected, interrogated by me, 
in 28 (87-5 per cent.) the disease did not begin until a year or more after 
the cessation of child-bearing, the average interval between the cessation 
of child-bearing and the onset of the disease, in these cases, being no 
less than 12-3 years. 

Only rarely does cancer of the uterus arise during pregnancy (6 in 
97 cases, or 6-2 per cent.) ; and within a year after parturition its occur- 
rence is equally rare (6 in 97 cases). 

These facts corroborate my contention, as to the independence of the 
outbreak of the disease, of the incidents of the reproductive life. 

Here it must be mentioned, that the subjects of cancer of the corpus 
uteri are much less prolific, than those with cervical cancer. 

Of 31 cases of this kind tabulated by Pichot, Ruge "and Veit, 14 
(45 per cent.) were absolutely sterile and 3 had only 1 miscarriage each ; 
while the remaining 14 had between them 57 children : thus, of these 
31 women, the average progeny was only 1-7 children each. When we 
recollect the comparatively late age at which this form of the disease 
supervenes, the significance of these figures is enhanced. 

As I have previously pointed out, the ensemble of facts relating to 
the life-history of the subjects of uterine cancer shows, that they have 



INFLAMMATION, TRAUMA, AND OTHER FACTORS 277 

almost invariably led regular, sober, and industrious lives. Personsjof 
drunken and dissolute habits are comparatively seldom affected. Of 
160 uterine-cancer patients consecutively under my observation, not a 
single one, so far as I could ascertain, had ever been addicted to prostitu- 
tion ; and, what is still more remarkable, only one presented undoubted 
signs of having had syphilis. 

In this connexion, the almost complete immunity of uterine-cancer 
patients from chronic ulcer of the leg, is worth noting ; among my cases 
there was not a single instance of it. 

According to Glatter, of 365 Vienna uterine-cancer patients, 91 (nearly 
25 per cent.) had been prostitutes ; but, it must be remembered, that he 
arrived at this conclusion in a rather peculiar way viz., by assuming 
that all those described in the registers as " Handarbeiterinnen," were 
as a matter of course " Lustdirne," which seems to be an unwarrantable 
assumption. At any rate, my experience in this respect is diametrically 
opposed to Glatter's conclusion ; and in this I am in accord with Ducha- 
telet, Lebert, Walshe, Winckel, Tanner and Schroeder. The high 
fecundity of uterine-cancer patients strongly favours my views ; for, a 
large proportion of prostitutes are sterile, or relatively infertile. 

Martin, Bruns and others, think that previous attacks of gonorrhoea, 
predispose cancer of the uterus ; but they have adduced no convincing 
arguments in support of this theory, which is at variance with all the 
information at my disposal. 

With regard to the influence of lacerations which may be associated 
with sub-involution, endometritis, hyperplasia, erosions, polypi etc. 
in the causation of uterine cancer, some gynaecologists have gone so far 
as to assert, that the disease always or frequently originates in them. 

In order to show the fallacy of this view, it is necessary to bear in 
mind the following facts about lacerations. They are usually confined 
to the inferior segment gf the uterus ; and at first labours they are of 
such frequent occurrence, as to be regarded by many gynaecologists as 
inevitable. Injuries of this kind are almost always multiple ; and in 
the majority of cases the lesion is bilateral, being most marked on the 
left side, opposite the situation usually occupied by the foetal occiput. 
In extent and depth they are variable, but in most cases the injury is 
only slight. The worst tears are met with after very rapid, tedious and 
instrumental labours. The occurrence of congenital cervical fissures, 
very like the traumatic ones, and in precisely similar situations, has 
been demonstrated by Fischel ; and it is probable that the latter are 
often confused with congenital flaws of this kind. 

Emmet and Ms followers regard lacerations as a veritable Pandora's 
box of uterine maladies ; in fact, the number of diseases they ascribe to 
this source, wellnigh exhausts the list. With regard to cancer, they 
even go so far as to assert, that in all cases the disease originates in 
lacerations. 

The only evidence adducible on behalf of these extreme views is the 
great frequency of lacerations ; which, of itself, is of course quite insuffi- 
cient, even when the two morbid conditions coexist. In cases of this 
kind, carefully observed by John Williams, in not a single instance 



278 THE NATURAL HISTORY OF CANCER 

did the cancerous disease appear to have started from the lacera- 
tion. 

Against any such theory it may further be objected ; that if uterine 
cancer really originated in lacerations, it would like the latter nearly 
always be multiple, and its precise seats of origin would correspond with 
the localities in which lacerations usuaUy occur ; but, in the initial mani- 
festation of the disease, none of these conditions are fulfilled. 

Moreover, against the assumed setiological importance of lacerations, 
is the fact ; that the interval between the laceration and the outbreak 
of cancer, extends over many years, and during this long period the 
uterus appears to be free from disease. 

Thus, the average age at which child-bearing commenced in my cases 
was 21-8 years ; whereas in the same women the average age at which 
uterine cancer supervened was forty-four years : thus, between the out- 
break of the disease and its alleged causation, a period of no less than 
,22-2 years intervened. 

Of like significance, as previously mentioned, is the long interval 
usually found between the cessation of child-bearing and the onset of 
cancer. 

Another indication pointing in the same direction, is furnished by 
the fact, that rapid, tedious and instrumental labours after which 
lacerations are commonest and most severe are relatively rare in uterine- 
cancer patients. 

Of 65 cases in my list, in which the character of the labours was 
noted ; in 59 they were natural (tedious or difficult in 9), and in only 6 
were they instrumental. 

Thus, notwithstanding many allegations to the contrary, no reliable 
evidence has hitherto been adduced, of any connexion between antecedent 
morbid affections of the uterus and cancer. 

The great majority of the patients under my observation, had been 
remarkably free from previous uterine disease of any kind. 

Of 137 cases in which special inquiries were made, only 13 had suffered 
from previous disease of the uterus ; viz., leucorrhoea 7, prolapse 3, and 
endometritis 3. 

This is in entire agreement with the facts previously mentioned, as 
to the good catamenial health of these patients, their remarkable fertility 
when married, and the ensemble of their life-history. 

Since this was written, it has been pointed out to me that West l had 
previously come to the same conclusion ; thus he says : "It may be 
supposed that we shall find indications of previous uterine disorder (as 
some suppose of uterine inflammation), out of which cancerous disease 
has been subsequently developed. Evidence, however, seems to be 
directly opposed to this supposition ; for, in the history of only 5 out of 
the whole 170 uterine-cancer cases, is there any mention of previous 
uterine ailment." 

The great rarity of cancer of the procident uterus is a fact of like 
import. Schmidt 2 reports that of 294 cases of cancer of the uterus 
under treatment at the Halle Clinic, only 2 were associated with pro- 
1 " Diseases of Women," 1864, p. 365. 2 Monats. f. Geb. u. Gyn., Bd. vii., Heft. 5. 



INFLAMMATION, TRAUMA, AND OTHER FACTORS 279 

lapse ; and of 423 women admitted for prolapse, only 2 were found to 
have cancer as well. 

These facts were well known to the great Cruveilhier, 1 who perti- 
nently remarks : " On doit s'etonner que le col uterin qui est si sou vent 
le siege de degeneration cancereuse, alors qu'il occupe sa situation nor- 
male, devienne si rarement malade dans le cas de prolapsus." 

Of similar import is the great rarity of cancer arising from uterine 
polypoid pseudo-plasms, of which comparatively very few cases have 
been recorded. 

Gastric Ulcer and Gastric Cancer. 

It is claimed by some practitioners, that most cases of gastric cancer 
originate from local ulceration. Thus, according to Mayo Robson, 2 
" Every cancer, whether external or internal, follows on a pre-cancerous 
condition, such as cancer of the gall-bladder on ulceration produced by 
gall-stones, cancer of the stomach on chronic gastric ulcer, epithelioma 
of the penis on irritation under a phimosis etc." I propose to show that 
these conclusions are untenable, being completely at variance with well- 
ascertained facts. 

Gastric cancer and gastric ulcer are such comparatively common 
diseases, that their not infrequent concomitance cannot be accepted as 
presumptive evidence of setiological relationship. 

The probability of any such causative connexion existing between 
the two maladies is contra-indicated, among other considerations, by their 
diversity in localization. 

Thus, cancer of the stomach, so frequently originates at the pylorus, 
that it is commonly spoken of as pyloric cancer ; analysis of 4,574 cases of 
gastric cancer (Brinton, Welch, Gurlt, Habershon, Luton and Fenwick), 
shows that in no less than 2,724 of these cases, or nearly 60 per cent., 
the disease was thus located. On the other hand, Welch's 3 analysis of 
793 cases of gastric ulcer, shows that only 95 or 12 per cent. were 
pyloric in situation. 

. According to these data then, the great majority of all pyloric cancers 
arise in a situation, where local ulcers are of great rarity ; and, conse- 
quently, they must usually be quite independent of any such antecedent 
lesion. 

Moreover, the commonest seat of gastric ulcer is the lesser curvature 
where 288 (36-3 per cent.) of Welch's 793 cases were located which is a 
rare situation for cancer, only 12-2 per cent, of Brinton and Welch's 
numerous cases, originating there. 

In like manner, the duodenum is frequently the seat of ulceration, of 
similar nature to that met with in the stomach, indeed, both of these 
localities are not infrequently concomitantly affected ; yet, cancer of the 
duodenum is one of the very rarest diseases : for of 7,297 primary malig- 
nant epithelial tumours tabulated by me, consecutively under treatment 
at several of the chief London hospitals, comprising 499 intestinal cancers, 
only 4 originated in the duodenum ; similarly, of 1,148 intestinal 

1 Anat. Path., liv., xvi. * Lancet, 1904, vol. ii., p. 1547. 

3 Pepper's " System of Medicine " (art. " Gastric Ulcer "). 



280 THE NATURAL HISTORY OF CANCER 

cancers, Ewald found that only 19 originated in the duodenum, and other 
statistical data are to the same effect. 1 

Another item pointing in the same direction, is the diverse sex inci- 
dence of the two maladies ; thus, while cancer of the stomach is of much 
greater relative frequency in males than in females, the female liability 
to gastric ulcer is largely in excess of that of males. 

In illustration of this, the following data are conclusive : the Registrar - 
General's Sixty-first Annual Report shows that 21-4 per cent, of the cancer 
mortality among males was due to gastric cancer, the corresponding figure 
for females being 13-2 per cent. ; with regard to gastric ulcer, of 177 con- 
secutive cases tabulated by me 2 as occurring among 32.505 male and 
28,175 female in-patients in London hospitals 117 were females,,and 60 
were males, showing that the liability of the former is more than double 
that of the latter ; and data collected by others are of similar import 
(Welch, Saundby, Bulstrode etc.). According to Saundby, 3 on the basis 
of clinical data, women are twenty times as prone to gastric ulcer as men ; 
and Bulstrode reports, that of 500 cases admitted into the London 
hospital, 1897 to 1902 402 were women and only 98 men. 

The age incidence of the two maladies is also very different, half of all 
gastric ulcers being met with between the ages of 20 and 30, and almost 
the whole of them being comprised between the years 18 to 38 ; whereas 
comparatively few gastric cancers are met with before 40, the average age 
at onset being 51 for males and 40-5 for females, most cases being com- 
prised in the decennium 50 to 60. 

Finally, it may be mentioned that the clinical symptoms associated 
with gastric cancer, are seldom indicative of antecedent ulceration ; for, 
cancer of the stomach runs a rapidly fatal course, the average duration of 
the symptoms seldom exceeding fifteen months. 

The cumulative weight of these diverse indications against there 
being, as a rule, any aetiological connexion between gastric ulcer and 
gastric cancer, is so overwhelming, as to be practically conclusive; 
although of course, I do not mean to deny that cancer may exceptionally 
originate from gastric ulcer. 



Gall-stones and Cancer of the Gall-bladder. 

The very frequent association of gall-stones, with that rare disease, 
cancer of the gall-bladder, has induced many practitioners to assume a 
causative relation of the former to the latter ; and, in reference to this 
presumption, Mayo Robson says : " The preventive treatment for 
cancer of the gall-bladder is obviously, removal of the source of irrita- 
tion." This conclusion seems to me without scientific warrant. To give 
it even some air of probability, it would be necessary to show that cancer 

1 Of 42,000 necropsies at Vienna hospitals, comprising 3,583 cases of cancer, of which 
443 were intestinal, only 7 originated in the duodenum (Schlesinger, Wien. klin. Woch., 
1898, Xr. 10, p. 245). Eighteen thousand necropsies at Guy's Hospital revealed only 10 
cases of primary malignant disease of the duodenum 6 sarcoma, 4 epithelioma (Perry 
and Shaw, Guy's Hospital Reports, 1894, vol. 1., p. 214). 
" Influence of Sex in Disease," London. 1885, p. 28. 

3 British Medical Journal, 1900, vol. i., p. 121. 



INFLAMMATION, TRAUMA, AND OTHER FACTORS 281 

of the gall-bladder is of fairly common occurrence ; whereas, in reality, it 
is one of the very rarest cancerous manifestations : thus of 7,297 1 cancer 
patients, under treatment in large London hospitals, I found that only 1 1 
had primary cancer of the gall-bladder ; Gurlt, 2 in Vienna hospitals, X 
reported only 5 instances in 11,131 cancer patients ; and Reiche, 3 from 
the mortality statistics of Hamburg, 48 cases (9 males, and 39 females) 
in 12,484 cancer deaths. 

Moreover, of 115 necropsies on persons with gall-stones, Mosher 4 
found only 2 affected .with cancer of the gall-bladder. 

In the face of these facts, it is surprising to find such a conscientious 
author as Rolleston, 5 stating that primary cancer of the gall-bladder " is 
by no means a rare disease," without adducing any evidence in support 
thereof. 

In like manner Robson says : " This disease is not nearly so uncommon 
as was formerly believed " ; but, in support of this pious opinion, not one 
jot or tittle of evidence is adduced. 

The great rarity of primary cancer of the gall-bladder, is thus shown 
to be an indubitable and incontrovertible fact. On the other hand, gall- 
stones are of frequent occurrence in the general community, Kehr and 
others having found them in about 10 per cent, of all adults, as deter- 
mined by post-mortem examination. It follows from these considera- 
tions, that gall-stones can very rarely be the cause of primary cancer of 
the gall-bladder, even if we suppose which is most unlikely in view of 
Mosher's data that every gall-bladder cancer is caused in this way. 

As I have elsewhere pointed out, 6 cancerous patients in general are 
more prone to gall-stones, than are the non-cancerous of the same age 
and sex in the community at large ; and Colwell 7 has recently estimated 
that the cancerous are two and a half times as prone to gall-stones as the 
non-cancerous, irrespective of the seat of the primary growth. 

I submit that the foregoing data only admit of one interpretation, 
viz., that cancer of the gall-bladder is seldom, if ever, caused by the gall- 
stones so often found associated with it. 

In cases of this kind, we must rather look to antecedent morbid con- 
ditions of the cystic mucosa, as being the determining factor of these 
concretions. 

It accords with this, that calculous concretions of the kidney and renal 
pelvis, which are of common occurrence, are hardly ever associated with 
malignant disease of these parts. 



Phimosis and Cancer of the Penis. 

With regard to the alleged causative connexion between cancer of the 
penis and phimosis, it is to be remarked that phimosis is one of the 
commonest anomalies ; and a very large proportion of the male population 
is'affected in this way, often to an extreme degree. 

1 Vide Chapter XVIII. 2 Arch. f. klin. CUr., Bd. xxv., S. 420. 

3 Deutsche mtd. Woch., 1900, Xos. 7 and 8. 

4 Johns Hopkins Hospital Bulletin, 1901, p. 253. 

6 " Diseases of the Liver," etc., 1905, pp. 620 and 627. a Chapter XVI. 

7 Middlesex Hospital Archives, 1905, vol. v., p. 148. 



282 THE NATURAL HISTORY OF CANCER 

If, therefore, as alleged, phimosis is a potent cause of cancer of the 
penis, this particular local variety of cancer should be very common. 

But, the ascertained facts show that it is far otherwise ; thus, of 2,669 
men with cancer, under treatment in the chief London hospitals, I found 
that only 106 had cancer of the penis ; and of 2,891 similar cases in Vienna 
hospitals, Gurlt found only 108 thus affected ; therefore, rather less than 
4 per cent, of these male hospital patients were affected with this variety 
of cancer. 

Englisch's statistics, 1 embracing a much larger number of cases 
namely 12,607 show that less than 2 per cent. (1-81) of all cancers in 
men, affect the penis ; the Registrar-General's Reports show that the 
rarity of cancer of the penis is much greater, than even these hospital data 
indicate ; for, of 9,685 men who died of cancer during the year 1900, only 
100 died of cancer of the penis, or about 1 per cent. ; Reiche's 2 Hamburg 
mortality data (1872-1898) show a still smaller proportion, viz., only 
17 cases in 4,906 male cancer deaths, or 0-34 per cent. ; while the United 
States Census Report, for 1900, shows that this local variety of disease is 
even rarer in that country ; since only 0-18 per cent, of the male cancer 
deaths were due to cancer of the penis. 

The United States negroes are said to be more universally and more 
severely affected with phimosis, than any other race ; yet, for the year 
1900 although the cancer death-rate of male negroes amounted to 
28-6 per 100,000 living not a single death from cancer of the penis was 
recorded during the whole year. This great rarity of cancer of the penis 
in negroes is fully confirmed by Rodman's 3 experience in Philadelphia, by 
the Louisville statistics, and by other independent testimony. 

Moreover, it is worth noting, that Jews are as little liable to cancer of 
the penis as non- Jews. 

If phimosis were really a potent cause of cancer of the penis, how very 
different all this would be. 



" Paget's Disease " of the Nipple and Areola, and Cancer of the Breast. 

Attention was first prominently directed to this subject by Paget's 
well-known essay on " Disease of the Mammary Areola preceding Cancer 
of the Mammary Gland," which was published in 1874. 4 

He reported cases in which initial lesions of this kind were, after 
various intervals, followed by the formation of cancer in the breast ; and 
the conclusion was drawn that this sequence " very often " happened. 
In this, there can be no doubt, Paget was mistaken. Indeed, he admitted 
that the areolar affection might often be cured, without any ill conse- 
quences ensuing ; and Velpeau had previously reported many instances of 
this kind. Paget adduced no statistical data in support of his dictum, as 
to the presumed frequency of the cancerous sequel, for none were then 
available. 

1 Allgem. wiener vied. Zeit., 1902, No. 16. 

2 Deutsche med. Woch., 1900, Nos. 7 and 8. ' 

3 " International Text-Book of Surgery," 1900, vol. ii., p. 734. 

4 St. Bartholomew's Hospital Reports, vol. x., p. 87. 



INFLAMMATION, TRAUMA, AND OTHER FACTORS 283 

Since then, however, the subject has been numerically investigated on 
a large scale ; and it has thereby been proved, that cancer of the breast 
follows " chronic eczema " of the nipple etc., in less than 1 per cent, of the 
total cases : thus of 5,440 mammary cancers tabulated by various authors, 1 
in only 41 (0-75 per cent.) did the disease begin in this way. Surgeons 
may therefore disabuse their minds of the idea, that " Paget's disease " 
plays an important part in the pathogenesis of mammary cancer. Areolar 
affections of this kind, which are rare, 2 are only exceptionally followed by 
the outbreak of mammary cancer ; consequently, the mamma should 
never be extirpated for lesions of this kind, unless signs of concomitant 
malignant disease are also present. 



" Lupous Cancer." 

Lately a great deal of attention has been given to this rare manifesta- 
tion, which has been cited as evidence of the belief, that " inflammation 
may slide into cancer." With regard to this suggestion we may at the 
outset remark, that although lupus and cancer are very common affections 
and fairly often concomitant, yet "lupous cancer " is certainly exceedingly 
rare ; it would be far otherwise if lupus had any special proclivity to 
cancer. Besides this, although lupus is a disease which supervenes in 
early life, cancer does not originate from it, until the patient has attained 
the cancer age ; the most therefore that can be legitimately claimed for 
lupus, as a factor in the causation of cancer, is that it imparts local tissue 
proclivity. Oftener than not, " lupous cancer " is merely a " scar cancer," 
the outcome of chronic lesions determined by cicatrization of the local 
disease, or of repeated injuries of the part by operative procedures. As 
is well known, in lupus and in the scars resulting from its erasion etc., 
histological appearances which are very " epithelioma-like," are usual, 
even in the absence of all cancerous manifestations. For further infor- 
mation relating to this subject, reference may be made to the publications 
of J. Hutchinson, 3 Bayha, 4 Steinhauser, Wild and others. 



Leucoplasia, Syphilis and Smoking, in Relation to Lingual and Buccal 

Cancer. 

In many parts of the body, such as the oral cavity, the outbreak of 
cancer is fairly often preceded by obvious hyperplastic changes leuco- 
plasia of the surface epithelia. 

Of 78 cases of lingual and buccal cancer, examined ad hoc by me, 5 
lesions of this kind pre-existed in 18 ; of 80 similar cases by Butlin, 6 in 

1 Bryant, Gross, Delbet, J. C. Warren, Bergmann, Shield, H. Morris, Campiche and 
Lazarus- Barlow. 

2 " Of 15,000 women examined at the gynaecological clinic, Chambers met with only 
two cases " (Transactions of the London Obstetrical Society, 1880, vol. xxii., p. 266). 

3 Archives of Surgery, October, 1890, p. 138. 

4 Bruns' Beitr. z. klin. Chir., 1887. 

6 Middlesex Hospital Surgical Report, 1888, p. 107. 
6 "Diseases of the Tongue," 1885, p. 265. 



284 THE NATURAL HISTORY OF CANCER 

16 ; and of 61 by H. Morris, 1 in 13 : thus of these 219 cases, leucoplasia 
pre-existed in 47, or in about 22 per cent. 

In the great majority of these cancer cases, there was no indication of 
any such antecedent lesion ; hence, it may be concluded that although 
leucoplasia predisposes to cancer, it is by no means a, necessary or even 
usual antecedent of this malady. 

Leucoplasia, according to Schwimmer, 2 is a rare disease ; for, of 5,000 
persons examined as to its presence only 20 were affected. It is of much 
more frequent occurrence in men than in women ; for, of Neisser's 547 
cases only 24 were women. 

Far too little is as yet known of the natural history of leucoplasia, to 
enable us to say in what proportion of cases it eventuates in cancer ; but, 
in an able investigation into this matter by the veteran Fournier, 3 of 
321 tabulated cases, 97 or 30 per cent., ended thus. Of course, many 
of these patients came under notice with the cancerous disease already 
developed ; so that it is impossible to say, that this percentage really 
represents the natural outcome of leucoplasia, as many slight cases would 
probably never apply for treatment. Hence it may be inferred that 
leucoplasia only exceptionally ends in cancer. 

It accords with this that leucoplasia is usually a very chronic affection ; 
and many cases have been recorded of from 25 to 45 years' duration, 
without having undergone any cancerous change ; of 12 instances of this 
kind in H. Morris' list, in 5 the duration of the disease had exceeded 
.10 years. 

Leucoplasia originates at a much earlier age than lingual cancer, for 
the average age at onset of H. Morris' 12 leucoplasia patients, was about 
thirty-nine years ; whereas, the average age for the onset of lingual cancer 
I have found to be about fifty-four years. This accords with Barker's 4 
results ; for, of 29 cases in which cancer followed leucoplasia, he found 
that the average interval was rather more than 14 years. 

It is thus noticeable that, even in patients with leucoplasia, lingual 
cancer does not supervene until about the age-period fifty to sixty, at 
which it usually eventuates in persons free from leucoplasia. 

According to Fournier, 80 per cent, of 324 leucoplasia patients had 
been infected with syphilis ; while, in the other 20 per cent, syphilis could 
be excluded. 

Of 88 cases of cancer of the tongue and mouth, in which I made special 
inquiries, there was evidence of previous syphilis in 31 ; and of H. Morris' 
58 cases in 12 : in the other cases syphilis could be excluded. 

From these figures, it is evident that syphilis plays a more important 
part in the causation of leucoplasia, than it does in lingual cancer. 

It is the same with tobacco-smoking, for this habit is far more con- 
ducive to leucoplasia " smoker's patch " than it is to cancer. 

Thus, of 247 leucoplasia patients, Fournier found that 97 per cent, 
were smokers ; 182 of these were syphilitic subjects, of whom 96 per cent. 

1 Transactions of the Medical Society, London, 1884, vol. vi. 

2 Transactions of the International Medical Congress, London, 1881, vol. iii., 
p. 171. 

3 C. R. Internal. Med. Cong., Paris, 1900. 

4 " Holmes' System of Surgery," 1883, vol. ii., p. 516. 



INFLAMMATION, TRAUMA, AND OTHER FACTORS 285 

were smokers ; and of 65 non-syphilitic subjects, 98-4 per cent, were 
smokers. 

Hence, though syphilis or smoking alone may cause leucoplasia, the 
combination of the two gives the greatest proclivity. 

With regard to the relation of smoking to cancer of the tongue and 
mouth, special inquiries made by me show, that of 77 cancer patients, 
12 had never smoked ; of the others, 41 had been great smokers, and 24 
moderate smokers, while 11 of the smokers had also chewed. 

The women of Western Europe seldom smoke, but this does not give 
them exemption from cancer of the tongue and mouth, although they are 
very much less prone to it than men. 

I have seen it stated that, but for syphilis and smoking, there would 
be no lingual and buccal cancer ; such facts as the foregoing show the 
absurdity of this statement. Besides, tobacco smoking was unknown in 
Europe prior to the discovery of America, while cancer of the tongue and 
mouth was then an old-established and well-recognized disease ; and, with 
regard to syphilis in its present form, most of those who have specially 
studied the subject believe, that it also came to us from America. In 
Finisterre, where women habitually smoke short pipes, Hertaux never 
saw a single case of oral cancer, although the disease is common among 
men ; and testimony to the like effect comes from other countries, where 
women have long been in the habit of smoking. 

Special inquiries made by me, as to the precise situation of the initial 
outbreak of lingual cancer, show that in nearly half (48 per cent.) of the 
total cases, the edge of the tongue is the part affected ; on the other hand, 
this is a comparatively rare site for leucoplasia, which in the great majority 
of cases affects the dorsum a situation in which lingual cancer very rarely 
originates only in about 5 per cent, of the total cases, according to my 
researches. 

Again, a common site for leucoplasia is the angle of the mouth ; but 
it is very rare for cancer to develop in this situation. 

From these facts it may be inferred that, even when leucoplasia and 
cancer coexist, the latter disease often originates elsewhere than in the 
leucoplasia patch. A case reported by H. Morris x strikingly illustrates 
this feature ; his patient had suffered from the papillary form of leuco- 
plasia, affecting the dorsum of the tongue, for several years, when epi- 
thelial cancer of the lower lip supervened. Moreover, leucoplasia has 
been known to develop, after the outbreak of cancer, as in cases reported 
by Shield and Butlin. 

From the consideration of the various items above set forth it may be 
inferred, that intrinsic causes are much more important factors in the 
origination of cancer than extrinsic ones ; which are by no means its 
necessary antecedents. In the vast majority of cases, the outbreak of 
this disease appears to be entirely spontaneous ; that is to say, it cannot 
be attributed to the immediate action of any appreciable extrinsic cause 
whatever. 

1 Transactions of the Medical Society, Ixtndon, 1884, vol. vi. (Case 14 in Table III.). 



286 THE NATURAL HISTORY OF CANCER 

Trauma and Cancer. 

Those who maintain that cancer is commonly caused by trauma 
must explain how it is that men, who suffer three times as often from 
traumata as women, are, nevertheless, only about half as liable to cancer. 

Thus, of 9,229 consecutive cases of trauma under treatment at four 
large London hospitals, I have found that 6,856 were males and 2,372 
females, or 2-89 males to 1 female. Similarly, of 240,063 deaths from 
traumata, tabulated by the Registrar-General for the twenty-five years 
1848-1872, 178,005 were males and 62,058 females, or 2-8 males to 1 
female. On the other hand, of 7,878 consecutive cases of cancer under 
treatment at the above-mentioned hospitals, 2,861 were males, and 5,017 
females, or 1 male to 1-7 females. Similarly, of the 19,433 cancer deaths 
in England and Wales during 1890, 7,137 were males and 12,296 females, 
or 1 male to 1-7 females. 

Evidently either these facts must be refuted, or the theory of the 
traumatic causation of cancer must be given up. 

Still more cogent is reasoning of this kind when applied to cancer of 
the breast ; for, whereas men are quite three times as liable to traumata 
of this part as women, yet they suffer from mammary cancer only in the 
proportion of 16 to 1,863, or 1 male to 116 females. 

Moreover, were mammary cancers thus caused, the nipple and areola 
would be more frequently affected than other parts of the breast ; but, 
as we have already seen, the actual proportion of cancers that arise from 
this part is less than 1 per cent., while the skin of the mammary region 
is even much less liable. 

This completely negatives the alleged causation of mammary cancer 
by pressure of the corset, injury of the nipple in suckling etc. 

Again, if the traumatic theory of cancer causation were true, those 
parts of the body most subject to injuries, such as the upper and lower 
extremities, the scalp etc., would be the commonest seats of the disease ; 
but its actual localization is totally different. 

The great rarity of malignant epithelial tumours of the extremities 
and scalp, has much significance in this connexion : thus, of my 7,297 
cancer cases, only 99 originated in the extremities (71 in the lower and 
28 in the upper) ; while there were only 10 scalp cases. Moreover, of all 
parts of the hand, the palm, which is most exposed to traumata, is least 
liable to cancer. 

Another item is, that the initial lesion of cancer is almost invariably 
solitary ; whereas, if the disease were of traumatic origin, it would often 
be multiple. 

It is a curious circumstance, that advocates of the traumatic theory 
of cancer causation should have overlooked these obvious facts. 

They base their belief in it on statements made by patients them- 
selves, as to the antecedent occurrence of trauma. Of 137 women 
with mammary cancer interrogated by me, 35 gave a history of ante- 
cedent trauma, or 25-5 per cent. ; inot her words, the most careful 
investigation directed expressly to this point, failed to elicit any previous 
history of trauma in 74-5 per cent, of all cases. 



INFLAMMATION, TRAUMA, AND OTHER FACTORS 287 

In not a single instance was there any evidence that the disease had 
developed out of induration, or other obvious lesion thus induced. 

In the cases under my observation, it seemed to me that injury was 
often merely the means of directing the patient's attention to the pre- 
viously existing disease, of which she had until then been unconscious. 

Of 1,000 cases of cancer consecutively under my observation, there 
was but a single instance in which the disease immediately followed an 
injury, and this was a case of so-called acute traumatic malignancy. 
Yet, if traumata were the efficient causes of cancer, such occurrences 
would be quite common instead of being so infinitely rare. 

Moreover, we cannot produce cancer by any kind of traumatism, 
even in those who are already subject to the disease ; and their wounds 
heal just as do those of the non-cancerous. 

The attempts made by Gilbert and Roger 1 to produce cancer of the 
mammae of old bitches, by subjecting them to various forms of mechanical 
irritation, completely failed to attain this end ; and Cazin, by rubbing 
soot into the irritated parts, was equally unsuccessful, although the soot 
was taken up by the local cells, as we know is also the case in " chimney- 
sweep's cancer." 

Though a blow, wound, or other injury may sometimes precipitate 
the formation of a cancer ; yet, it appears to me from the foregoing con- 
siderations, that such stimuli are of themselves inadequate to cause the 
disease. I regard the relation of trauma to cancer to borrow a Dar- 
winian simile as resembling that of a spark in contact with combustible 
matter, the result depending upon the nature of the latter rather than 
upon the spark itself. 

" Traumatic Malignancy." 

Among the clinical records of the last half -century, some rare instances 
may be found, in which the outbreak of malignant disease has appeared 
rapidly to follow severe local trauma (" acute traumatic malignancy "), 
as in cases reported by Barwell. 2 H. Cripps, Puzey and others. Careful 
study of the records of these rare cases all of which are sarcomata 
inclines me to admit the reality of this exceptional method of causation ; 
although, in some cases of this kind, the malignant growth undoubtedly 
antedated the alleged causative injury, as was the condition in the only 
example that has come under my own immediate notice. 

Another group of cases, nearly akin to the above, comprises sarcomata 
developing at the seat of recent fractures, of which examples have been 
recorded by Shattock, 3 Griffiths, 4 Senn, 5 Haberen, 6 Pollard,? Virchow, 8 
and others. In some cases of this kind of which I have elsewhere 
reported an example 9 the tumour preceded and was the cause of the 

1 La Presse Med. de Paris, July 14, 1894. 

2 British Medical Journal, 1882, vol. i., p. 187, et seq. 

3 Transactions of the Pathological Society, London, 1896, vol. xlvii., p. 261. 
* British MedicalJournal, 1884, vol. i.. p. 1125. 

5 " Pathology and Surgical Treatment of Tumours," 1900, p. 85. 

6 Arch. f. Mm. Chir., Ed. xliii., S. 352. 

7 Transactions of the Pathological Society, London, 1885, vol. xxxvi., p. 388. 
" Path, des Tumeurs," 1867. t. i., p. 482. 

9 Middlesex Hospital Surgical Report for the Year 1888, p. 269, No. 4. 



288 THE NATURAL HISTORY OF CANCER 

fracture, rather than vice versa. In other cases, however, the disease 
probably started from tumour germs, entangled in the reparative new 
formation, and incited thereby to abnormal growth (" callus-sarcomata " 
etc.). 

From the fact that cartilaginous structures commonly abound in 
these tumours, it may be inferred that heterotopic elements of this kind 
are the germs whence most of them arise ; and it accords with this, that 
some of these tumours are of an osteo-chondromatous, rather than of a 
sarcomatous, nature. 

In like manner, hydatid and tuberculous diseases, sometimes develop 
in the callus of fractures. 

Even many years after the original injury, malignant tumours have 
been known to originate thus. 

In other parts of the body similar conditions are very exceptionally 
met with ; e.g., cancer originating in Rontgen-ray burn (C. W. Allen, 
Foulerton etc.), in an issue wound (Billroth), in an empyema wound 
(Young), in the wound after the operation of ventro-fixation of the uterus 
(Malone), in the scar of stumps after amputation, in old scars (especially 
of burns), in chronic sinuses etc. 

In like manner, after the surgical ablation of non-malignant tumours, 
in very rare and exceptional cases, malignant disease may spring up in 
the wound : e.g., after removal of mammary fibro-adenoma (Erichsen), 
of simple dermoid cyst (Wolf), of " desmoid " of the abdominal wall 
(Asken), of angioma (Pirogoff), of uterine myoma etc. 

It is only after operations in which one or both ovaries have been 
removed, that occurrences of this kind are at all frequent ; and this type 
of case, setiologically regarded, belongs to quite a different category, as 
I shall subsequently have occasion to show. 

I have also seen instances of the acute outbreak of malignant disease, 
after the surgical removal of fairly chronic cancers of the breast, uterus, 
cheek etc., in which it seemed likely that the acute post-operative exacer- 
bation of the malady, might be ascribed to dissemination in*fche wound 
of particles of the disease, detached during the course of the operation, 
which had thus acquired increased capacity for malignant growth. 

Perhaps the most remarkable feature about such cases as are com- 
prised in this section, is their great rarity ; to account for this, I can 
only surmise that the final outbreak is but the explosion of a long train 
of antecedent preparation ; hence also the failure of attempts to repro- 
duce similar results experimentally in animals. 



CHAPTER XII 

THE QUESTION OF THE ORIGIN OF MALIGNANT FROM 
NON-MALIGNANT TUMOURS 

IMPORTANT practical issues are involved in the solution of this question,, 
as to the alleged proclivity of non-malignant tumours to become malig- 
nant. If any such tendency really exist, then non-malignant .tumours 
ought to be promptly extirpated. 

Prior to the application of the microscope to the study of new growths, 
it was generally believed that every chronic tumour (" scirrhous ") either 
was malignant or tended to become so. This dictum was long ago 
stigmatized by Lebert 1 who showed its erroneousness as : "A very 
convenient doctrine for surgeons "; and, as I shall proceed to show, this 
criticism still holds good. 

The difficulty of then discriminating between malignant and non- 
malignant tumour-like swellings, rendered some such belief inevitable ; 
but, since the utilization of the microscope for this purpose, it is sur- 
prising to find the old creed still so influential. 

We now have to inquire whether, in the light of modern research, this 
belief is justifiable. 

Since innocent tumours may inflame, suppurate, ulcerate, necrose, 
and degenerate, just like physiological parts of the body, it seems not 
unreasonable to suppose, on a priori grounds, that they may also become 
the seats of malignant disease. The occasional coexistence in the same 
organ, of benign and malignant tumours, favours this view. Such are 
the chief considerations which have given rise to the common belief, that 
innocent tumours are peculiarly apt to become malignant. 

On critical examination of the subject, two considerations have much 
impressed me. 

The first is the rarity with which these two kinds of neoplasms coexist 
in the same organ ; so that, even if we admit that malignant transforma- 
tion takes place in all such associated neoplasms, the event must be one 
of great rarity very much rarer than it would be, if non-malignant 
tumours were especially prone to become malignant. 

The second consideration is the inconclusiveness of the evidence, as 
to the malignant growths in most of these cases, having sprung from their 
non-malignant associates. In many instances, it is perfectly evident, 
that the association is a mere coincidence, each neoplasm having originated 
independently. In other cases, the coexisting neoplasms are more closely 

1 " Traitedes Maladies Cancereuses," Paris, 1851, p. 59. 
289 19 



290 THE NATURAL HISTORY OF CANCER 

associated ; but, even in these, the appearance of the non-malignant 
tumours is often such, as hardly to countenance the belief that the 
malignant disease had sprung from them. 

In short, a thorough examination of the subject in all its bearings has 
convinced me, that non-malignant tumours have no special proclivity 
to malignancy. 

In support of this thesis, I now propose to discuss the evidence in 
detail, as it affects some of the more important organs. 



Uterine Myoma and Malignant Disease. 

It must be borne in mind that uterine myomata are of very frequent 
occurrence, according to Bayle, 20 per cent, of all women over thirty- 
five are thus affected ; and there are good reasons for believing, that the 
liability to these tumours increases still more with advancing years. 1 

If this estimate be correct and so far as I can judge it is not very 
wide of the mark these neoplasms are much commoner even than cancer 
(malignant epithelial neoplasm). Hence, considering the great frequency 
of both diseases in women of a certain age, we need not be surprised to 
find them coexisting in the same uterus rather frequently. Thus, of 
78 uterine-cancer necropsies of my list, in 5 there were concomitant 
myomata ; and of the 45 similar necropsies tabulated by Lebert, 6 were 
associated with myomata ; thus, in these 123 uterine-cancer necropsies, 
myomata co-existed in 11, or in 9 per cent. 

In estimating the significance of this concomitancy, the following 
items demand special attention. 

1. In the immense majority of cases in four-fifths of those under 
my own observation 1 the two neoplasms were quite separate and inde- 
pendent of one another the myoma having sprung from the corpus and 
the cancer from the cervix or portio so that, in these cases, there could 
be no question of the latter disease having originated from the former. 

2. In the remaining cases, the coexisting neoplasms were more closely 
associated, most of them arising in the corpus. A common condition is 
to find one or more small subperitoneal or intra-mural myomata, with 
cancer of the mucosa. Under these circumstances, the fibroid is seldom 
cancerous. Of course, when the cancerous disease spreads widely, even 
fibroids such as these may be at length invaded. 

3. A good many instances have been recorded of myomata projecting 
into the uterine cavity, and bearing on their surface a cancerous growth 
or ulcer. In cases of this kind, the cancerous disease usually spreads 
from the mucosa to the fibroid, by the way of the peri vascular lymphatics. 
In like manner, uterine fibroids projecting into the abdomen, sometimes 
become cancerous through extension of the disease from adherent neigh- 
bouring organs, such as the ovary, intestine, and omentum. 

4. There is yet another way in which fibroids may possibly be secon- 
darily invaded by cancer, and that is by dissemination from a primary 
focus elsewhere, of which Schaper 2 has reported an instance, the primary 

1 Vide the author's book on " Uterine Tumours," 1901, p. 123. 

2 Arch. f. path. Anat., 1892, Bd. cxxix., S. 61. 



MALIGNANT FROM NON-MALIGNANT TUMOURS 291 

disease being in the lung, and Bender * a similar case, secondary to primary 
cancer of the mamma. 

5. In such cases as the foregoing there is, of course, no question of 
the cancerous disease having primarily originated in the myoma. Indeed, 
this is an event of such rarity, that the great Cruveilhier, with his large 
and carefully recorded experience, never saw a single instance of it : 
hence he wrote : 2 " Les corps fibreux ne sont pas susceptibles de degenera- 
tion cancereuse. II y a incompatibility absolue entre les corps fibreux 
et le cancer." Although we now know, that there is no such absolute 
incompatibility between uterine myoma and cancer, as Cruveilhier 
believed ; yet, the extraordinary rarity of this morbid conjunction, is a 
noteworthy and well-determined fact. Thus, notwithstanding the great 
activity of modern pathologists, only about two dozen instances of it 
have hitherto been recorded ; 3 and, in many of these, the evidence 
adduced as to the cancer having originated in this particular way, is 
far from being really convincing. 

The frequent presence of epithelial structures in uterine myomata, as 
first demonstrated by Babes and Diesterweg, and confirmed by Ricker, 
Orloff, Recklinghausen, Landau etc., enables us to understand the source 
whence the cancerous disease of uterine fibroids originates. 

Cases of this kind have been described by Klob, Coe, Rcahrig, Lieb- 
mann, Legueu and Marien, Roily 4 etc. 

Klob, 5 in describing the first case of this kind, says : " In 1862, a sin- 
gular specimen was added to the Salzburg Museum. From the interior 
of a fibroid, the size of a child's head, situated in the posterior wall of the 
uterus, carcinoma had undoubtedly developed, without any other portion 
of the uterus being affected ; and, I am therefore constrained to admit the 
possibility of such a transition ; although I cannot recall a second case of 
this kind, either in the literature of the subject, or in my rather extensive 
experience." 

In a case under my own observation, there was a large, encapsuled, 
fibroid tumour, the size and shape of a lemon, in the substance of the 
lower part of the posterior wall of the uterus, where it had compressed the 
rectum, and caused symptoms of intestinal obstruction. This tumour 
was infiltrated throughout by colloid cancer of the tubular type, which 
had also slightly invaded some of the adjacent structures. Several 
adjacent lymph-glands were invaded, but there were no metastases. The 
patient was a woman, aged forty-three, who had complained of difficulty 
in defsecation for the last twenty-five years. 

Noble, 6 having analysed 1,188 promiscuously-gathered myoma cases, 
found that 29 of them were complicated by cancer of the corpus and only 
12 by cancer of the cervix ; this ratio being so much at variance with the 
usual standard of uterine-cancer localization, he concluded that myomata 
predisposed to cancer of the corpus. If his cases were really represen- 

1 Butt, et Mem. Soc. Anat., Paris, October, 1904. 

2 " Traite d'Anat. Path. Gen.," etc., liv. iii., p. 661. 

3 Piquand, " Les Degenerescences des Fibro-myomes de 1'Uterus," Paris, 1905. etc. 
* Anat. f. path. Anat., 1897, Bd. ol., S. 555. 

8 " Path. d. weibl. Geschlechtsorgane," 1864, S. 163. 
6 American Medicine, September 10, 1904. 

192 



292 THE NATURAL HISTORY OF CANCER 

tative, such a conclusion would be legitimate ; but we know that cancer 
of the cervix is an easily diagnosed disease, and it is not likely that many 
patients thus affected would be sent to the surgeon to be operated on 
for myoma. This is undoubtedly the explanation of the paucity of cases 
of cancer of the cervix comprised in his list ; hence his conclusion must 
be rejected, as being essentially misleading. 

If such conditions were of common occurrence, cancer of the uterus 
would be more frequently met with in the corpus than elsewhere, for it is 
here that over 90 per cent, of all uterine myomata originate ; but we know 
that only about 5 per cent, of uterine cancers arise from the corpus. 

It follows from what has been stated that, far from uterine fibroids 
having any special proclivity to become cancerous, they are very much 
less prone to originate this disease than are the epithelial elements of the 
uterus itself. 

Some pathologists have ascribed the association of cancer with uterine 
fibroids to " irritation," excited by the presence of the latter and the 
consequent hyperplasia of the mucosa. 

Thorn l has reported an instance of this kind, in which the cancerous 
disease appeared to have been caused by the presence of a large calcified 
fibroid. If this alleged causation were of common occurrence, we should 
expect to find fibro-myomata more often concomitant with uterine cancer, 
than with any other local variety of cancerous disease. 

But this is not so, for myomata coexist with uterine cancer only in 
9 per cent, of the necropsies ; whereas, I have found that they coexist 
with cancer of other localities, to the extent of 18-5 per cent, 2 It is 
evident, therefore, that the changes excited in the uterine mucosa etc., 
by the presence of myomata, do not specially predispose to cancer. 

Passing now to the consideration of the alleged proclivity of uterine 
myomata to become sarcomatous, the first fact that strikes me is, the 
great frequency of the former and the great rarity of the latter disease. 
My analysis of 2,649 consecutive cases of uterine neoplasms shows 883 
uterine fibro-myomas, and only 2 sarcomas. In Gurlt's analysis of 4,115 
uterine neoplasms, the proportion of fibroids to sarcomas is as 481 to 8. 

It is evident from these data, that uterine myomata seldom become 
sarcomatous. 

This is quite in accord with the experience of operators, who have 
found that only from 2 to 4 per cent, of their cases were complicated by 
sarcoma. Of course, even this proportion of malignant cases, is far in 
excess of the average for myomata in general ; for, the cases comprised in 
this estimate, were specially selected as requiring operative treatment. 

Among those who have recorded series of cases of this kind, reference 
may be made to Evelt's 3 table of 120 operations, with 3 examples of 
sarcoma ; to Fleischmann's 4 130 cases, with 5 examples of sarcoma ; to 
Hauber's 5 138 operations, with 3 examples of sarcoma ; to Ulesko- 

1 Zeite. f. Geb. u. Gyn., 1893, Bd. xxviii., Heft 1. 

2 Of 44 breast-cancer necropsies, I found uterine fibroid in 5 ; and of 37 necropsies 
for cancer in other localities fibroids were present in 10 cases. 

3 Monats. f. Geb. u. Gyn., November, 1903. 
* Wien. med. Woch., 1906, Bd. Ivi. 

6 Zent. f. Gyn., 1904, No. 11. 



MALIGNANT FROM NON-MALIGNANT TUMOURS 293 

Stroganowa's l 100 cases, with 10 instances of malignant disease ; to 
Runner's 2 100 cases, with 7 examples of malignancy ; to Cullingworth's 3 
100 cases, with 1 example of malignancy ; to Flatau's 4 104 operations, 
with 5 instances of sarcoma ; to Fehling's 5 series of 409 operations, with 
9 sarcomata ; to Martin's 6 205 cases, with 4 sarcomata etc. : thus, of these 
1,406 operated myomata, 39 or 3-3 per cent, were sarcomatous. 

I have seen it stated, that cystic myomata are more prone to originate 
sarcoma than their solid congeners ; but, I believe this is due to cystic 
sarcomata and myomata, being easily mistaken for true cystic myomata. 

It is thus quite clear, that the origin of sarcomatous disease from myo- 
matous tumours, is very much rarer than it would be, if these tumours 
really had any special proclivity that way. 

Nevertheless, the fact of the occasional origin of sarcomatous disease 
in uterine fibro-myomata, has been clearly established by many well- 
recorded examples. 

In this connexion, it must be remembered that myomata are of com- 
posite build, including connective tissue, muscle elements, bloodvessels, 
and lymphatics, any of which may be comprised in the sarcomatous 
matrix. Hence corresponding varieties of the disease. Thus, when the 
morbid process centres in the connective tissue, its elements multiply, 
destroying the adjacent fibrous tissue, muscle cells etc. (myosarcoma, myo- 
myxoma etc.) ; when the bloodvessel and lymphatic elements are chiefly 
involved, we get telangiectasic (myosarcoma telangiectaticum), and lym- 
phangiectasic varieties (myosarcoma lymphangiectaticum). In other 
instances the muscle elements are alleged to be primarily affected, and to 
increase at the expense of the remaining constituents (myoma levicellulare 
malignum). In their recurrences and metastases, each of these varieties 
usually breeds true. 

The occurrence in these tumours of cartilaginous, osseous, and other 
heterotopic structures, of which many instances have now been reported 
(Ascher, Feuchtwanger, Kworostansky, Freund, Bidder etc.), seems to 
indicate that this form of sarcomatous disease may often be of pre-patal 
origin. 

Myomata of the uterine wall may also, very rarely, be secondarily 
invaded by sarcomatous disease of the overlying mucosa, of which 
Whitridge Williams has reported an instance. 

It follows from what has been stated, that the possibility of benign 
uterine tumours taking on malignant characters cannot be denied ; but 
this is a very different thing from admitting, that such neoplasms are 
specially prone to become malignant. This is disproved by the great 
rarity of the coincidence. Non-malignant uterine tumours, have no 
special proclivity to malignant disease ; on the contrary, as I have shown, 
they are much less prone to originate such changes, than are the morpho- 
logical elements of the uterus itself. 

Monats. f. Oeb. u. Gyn., September, 1902. 

Am. Med., July 11, 1903. 

British Journal of Obstetrics and Gynaecology, January, 1902. 

Munch, med. Woch., 1901, No. 14. 

Beitr. z. Oeb. u. Gyn., 1898, i., S. 485. 

Arch. f. Gyn., 1888, Bd. xxxii., S. 470. 



294 THE NATURAL HISTORY OF CANCER 

Mammary Adenoma and Malignant Disease. 

After the non-malignant adenomata (" chronic mammary tumours ") 
had been clearly differentiated from malignant tumours of the breast by 
Astley Cooper, the partisans of the old belief as to the special proclivity 
of the former to become malignant, still persisted in the old creed. Cooper 
himself admitted the possibility of such an occurrence, thus he says : x 
" I believe that if a person has a tumour of the breast which is not 
malignant, and that it remains so till the change of life takes place ; that 
then an undue action may be excited in the part, and the tumour become 
scirrhous." 

In order to determine the ratio in which epithelial cancer arises from 
non-malignant mammary tumours, I have consulted the records of 254 
consecutive cases of mammary cancer, of which I have preserved 
detailed reports : I find that, in this series, cancer originated in connexion 
with fibro-adenoma in only two instances. In other words, for every 
case of cancer that had originated, under circumstances suggestive of its 
having .sprung from a fibro-adenoma, there were 126 cases that had 
evidently originated otherwise. 

Now I have ascertained that the relative frequency of the occurrence 
of fibro-adenomatous and cancerous tumours in the female breast is 372 
to 1,863, or the ratio is about 1 to 5. 

It is evident from these data, that the malignant transformation of 
fibro-adenomata is an event of extreme rarity very much rarer than it 
would be, if fibro-adenomata had any special proclivity to become 
cancerous. 

Even when mammary carcinoma is found in association with a non- 
malignant tumour of the part, the cancerous disease often appears to 
have originated quite independently of the latter, as in cases reported by 
Paget, 2 Bryant, 3 Richet, 4 Gross, 6 Waldeyer 6 and others. I have met with, 
and elsewhere described, 7 two somewhat similar cases. 

Many instances of the origin of sarcoma in association with mammary 
fibro-adenoma, have now been recorded. Some authors even maintain, 
that most sarcomata of the breast arise in this way, rather than from the 
tissues of the gland itself ; thus, of eight cases specially studied by Labbe 
and Coyne 8 ad hoc, four of them appeared to have originated from old 
adenomata. I have not met with such cases in anything like such a 
large proportion ; for, among thirty sarcomata of the breast specially 
studied by me, there was only one instance in which the malignant 
affection arose in this way. Hence, I feel bound to reject Labbe and 
Coyne's conclusion, which appears to be based upon too narrow an 
experience. In some of these chronic mammary tumours, we probably 

" Lectures on Surgery," 1839, p. 378. 
" Lect. Surg. Path.," 1853, vol. ii., p. 259. 
" Diseases of the Breast," 1887, p. 339. 
Le Practicien, 1879, No. 14, p. 163. 
"Am. Syst. Gyn.," vol. ii., p. 207. 
Arch. f. path. Anat., Bd. lv., S. 124. 
" Diseases of the Breast," p. 312. 
8 " Traitedes Tumeurs benignes du Sein," pp. 290 and 36c t 



MALIGNANT FROM NON-MALIGNANT TUMOURS 295 

have to do with sarcomatous disease, starting from overgrown super- 
numerary mammary sequestrations, as I have elsewhere indicated. 1 

From what has been stated, it may be concluded that non-malignant 
mammary tumours, like their uterine congeners, have no special proclivity 
to originate malignant disease. 



Ovarian Cystoma and Malignancy. 

The question of the frequency of malignancy, as a complication of 
ovarian cystomata, has been much debated among practitioners ; but, 
as the matter has seldom been studied with the aid of adequate statistical 
data, very little has been done to dissipate the prevailing obscurity and 
confusion. 

In approaching this tangle with the object of getting at the truth, the 
first item that strikes me, is the great frequency of these non-malignant 
ovarian cysts ; and the great rarity of any form of malignant disease of 
ovarian origin. 

For instance, of 9,701 cases of tumours in women, under treatment 
at several of the chief London general hospitals during a succession of 
years, I found that 4,036 had non-malignant tumours, of which 635 were 
ovarian cysts, or 6-5 per cent, of the total ; whereas, 5,665 had malignant 
tumours, of which only 67 were ovarian, or 0-69 per cent, of the total. 

Gurlt's analysis 2 of 7,776 cases of malignant disease in women at the 
chief Vienna hospitals, points to the same conclusion ; for, in only 78 of 
these patients, or in 1 per cent., did the disease originate in the ovary. 

If further evidence as to the comparative rarity of malignant disease 
of the ovaries is required, reference may be made to the national mortality 
returns ; thus, the Sixty-third Annual Report of the Registrar-General, 
shows that of 15,588 women who died of malignant disease during the 
year 1900, the ovary was the part affected in 275 cases, or in 1-7 per cent. ; 
and the United States national statistics for the same year, show a still 
smaller proportion of malignant ovarian disease viz., less than 1 per 
cent. (0-9). 

The obvious inference from these data is, that non-malignant ovarian 
cystomata seldom originate malignant disease, and this conclusion 
accords with the clinical evidence, as furnished by the record of long series 
of operated cases by individual surgeons : thus, of 1,388 ovarian tumours 
operated on by the surgeons of the Johns Hopkins Hospital, Swan found 
that only 41 were malignant, or about 3 per cent. ; and Geyer, for 
the Wiirtzburg clinic, gives the percentage of malignancy as 2-3. , 

Here it seems desirable to point out that ovarian cystomata comprise 
several different varieties of tumours, among which it is in this connexion, 
necessary to discriminate and set aside for separate consideration, the 
papilliferous and dermoid forms. 

It may be taken as proved, that malignant disease may exceptionally 
arise from each of the different varieties of cystomata ; but, some of them 
appear to have greater proclivity in this direction than others. 

1 " Diseases of the Breast," p. 73, etc. 

2 Arch. f. klin. Chir., 1880, Bd. xxv., S. 420. 



296 THE NATURAL HISTORY OF CANCER 

The papilliferous ovarian tumours or at any rate a considerable 
proportion of them are marked off from the other varieties, by the fact 
that they manifest contagious properties, 1 that is to say, they often 
become diffused throughout the peritoneal sac by auto-implantation of 
detached fragments ; hence their recurrence after removal in situ, or in 
some part of the operation wound, is frequent. Moreover, the disease is 
generally bilateral in over 68 per cent, of the total cases, according to 
Pfannenstiel. It is necessary to distinguish this form of local diffusion, 
from the very different generalization of malignant disease, with which 
it is undoubtedly often confounded. It is probably owing chiefly to this 
cause, that papilliferous ovarian tumours have acquired a special reputa- 
tion for malignancy ; 2 and the fact that primarily-arising ovarian cancer, 
sometimes assumes the papillary form ab initio, has tended to the same 
end. 

When due allowance has been made for these sources of error, it is 
doubtful whether there is any justification for the general belief, in the 
special proclivity to malignancy, of these papilliferous tumours. The 
researches of Pfannenstiel, 3 Semb 4 and others, specially point to this 
conclusion ; with which the fact that papillomata in general, manifest no 
such proclivity, also accords. 

The rather numerous cases reported in comparatively recent times, of 
the supervention of malignant disease in both its epithelial and con- 
nective tissue forms in connexion with dermoid and teratoid ovarian 
tumours, suggest that these formations may have special proclivity that 
way ; but, in the absence of the requisite numerical data, nothing more 
definite can be said. 

With regard to the other and commoner varieties of ovarian cysts, 
which after all comprise the great majority, there is a consensus of opinion, 
that they have no special proclivity to malignancy ; and this accords with 
the data revealed by my statistical research, as previously mentioned. 
When therefore it is stated that, from a practical standpoint, "all 
ovarian tumours must be regarded as malignant until removed and 
proved otherwise," I reply that, although this may be "a very con- 
venient doctrine for surgeons," it is certainly not in conformity with the 
facts revealed by a scientific examination of the subject. 

In other parts of the body, where I have specially studied the question, 
I have found that this conclusion is equally valid. 

In like manner Semon 5 reports, that of 10,747 non-malignant, intra- 

1 The ensemble of the characters of these growths indicate their affinity with the 
genital condylomata ; and, like the latter, they are probably transmitted during sexual 
intercourse, either with or without some other venereal malady, such as gonorrhoea, 
syphilis, etc. To this it may be objected that, although growths of this kind are recog- 
nized as occurring in the vagina, portio, and tube, they have never been met with in the 
uterus. The answer is that these lesions also occur in the uterus, where they are com- 
monly confounded with certain hypertrophic forms of chronic endometritis, adenoma, 
and even, in rare cases, with villous cancer, etc. In this connexion we must remember 
that it is only in comparatively recent times thanks to the publications of Doran, 
Doleris, etc. that the occurrence of similar papillomatous growths in the Fallopian 
tubes has been discriminated ; and even now the identity of the latter with condylomata 
is not recognized by gynaecologists. 

2 Gebhard, " Path. Anat. d. weibl. Sexualorgane," 1899, S. 356. 

3 Veit's " Handb. d. Gynakologie," 1898, Bd. iii. 

* Norsk. Mag. f. Laegeridensk, October, 1896. 5 Cent. f. Chir., 1890, S. 463. 



MALIGNANT FROM NON-MALIGNANT TUMOURS 297 

laryngeal neoplasms, whose history had been studied by him, there 
were only 47 instances in which malignant disease had supervened. 

It follows from what has been stated, that the possibility of benign 
tumours subsequently developing malignant characters, has been 
thoroughly proved ; but this is a very different thing from admitting 
that such tumours are specially prone to malignancy. This is disproved 
by the extreme rarity of the coincidence. Non-malignant tumours are, 
in fact, less liable to originate malignant disease, than are the normal 
morphological elements of the body itself. 



CHAPTER XIII 

MULTIPLE PRIMARY CANCER ; AND THE ASSOCIATION OF 
CANCER WITH OTHER TUMOURS 

A PECULIAR feature of cancer is, that the initial lesion is generally solitary. 
The researches of Hauser and Petersen into the architecture of small 
cancerous nodules, by serial sections and reconstruction models, show 
that the disease spreads in a multicentric manner, each ingrowing column 
being an outgrowth from the original germ, and therefore at first con- 
tinuous with it. It is now, however, generally recognized, that excep- 
tionally the disease springs up from more than a single original germ ; 
and it is this that constitutes primary multiplicity, as the term is here 
employed. 

Pathologists have been aware of this for some time, although it is 
only recently that the subject has attracted special attention. Such 
cases, however, are decidedly rare. 1 The wonder is that they do not 
occur more frequently, especially if as alleged cancer is a parasitic 
disease. By some, however, this peculiarity has been taken to indicate 
analogy with certain specific diseases, the virus of which when intro- 
duced into the system confers immunity for a longer or shorter period. 
The ensemble of the indications, as previously mentioned, is, however, 
decidedly against the acceptance of this suggestion. 

Such indications seem to me rather to imply, that the solitariness of 
the initial lesion of cancer is, in its origin, akin to the solitariness of most 
non-malignant tumours, and developmental anomalies per excessum. 

At any rate, it is worth noting in this connexion, that all non-malignant 
tumours are occasionally multiple in origin ; and some of them, such as 
uterine myomata, frequently manifest initial multiplicity. 



Bilateral Manifestations. 

Among the numerous cases of the multiple outbreak of malignant 
disease lately reported, some of the most striking are those in which the 
malady arises concurrently in both of paired organs, or in both of other 
bilaterally symmetrical parts of the body. These bilateral tumours are 
often described as symmetrical : but, it is very seldom that the con- 
comitant tumours correspond so exactly, as to justify the use of this term. 

1 Of 1,664 cases of mammary cancer tabulated by Gross, only 2 were bilateral in 
origin ; but Billroth met with 3 instances of this kind in 245 mammary cases ; 
according to Nicholls, of 685 necropsies for cancer in Montreal hospitals, 18 showed initial 
multiplicity. 



MULTIPLE PRIMARY CANCER 299 

A considerable proportion of bilateral malignant tumours are met with 
in early life, and are of congenital origin, many of these obviously arising 
in connexion with gross developmental lesions. In other cases of this 
kind, there is often evidence of the malignant disease having supervened 
on some antecedent morbid condition, such as eczema, seborrhoea etc. 

Non-malignant tumours of bilateral origin, are even less exceptional 
than their malignant congeners. 

Of course care must be taken to discriminate these primarily arising 
bilateral malignant tumours, from secondary forms, due to bilateral dis- 
semination from a remote primary source, e.g., stomach, thyroid, prostate 
etc., as also from local disseminative lesions, whether continuous or dis- 
continuous ; and this is sometimes by no means easy. 

Subjoined I submit a few remarks, as to the leading features of some 
of the chief local varieties of these bilateral outbreaks. 

Mamma. I have elsewhere described 1 an example of bilateral cancer 
of the female breast ; and referred to similar cases by Aitken, Volkmann, 
Klotz, Terrillon and others. In all of these instances, the malady was 
concomitant with the puerperal state, its onset was acute, and its pro- 
gress very rapid ; hence Klotz has described the condition as " Mastitis 
carcinomatosa gravidarum et lactantium." Billroth 2 has described an 
instance of acute bilateral sarcomatous disease of the breast, in a preg- 
nant woman. This type of malignant disease seems to be relatively less 
rare than^the epithelial form ; for, of Gross's 156 cases of mammary sar- 
coma, 3 were bilateral. 

Mammary fi.bro-adenom.ata may also be bilateral, for of 46 cases 
studied by me, in 1 instance there were several small tumours in both 
breasts ; and of Velpeau's 54 cases, 5 were bilateral. 

It is by no means rare to see cancer of one breast followed, after a 
time, by outbreak of the disease in the other. The great majority of 
these cases are, however, due to direct extension of the primary disease, 
or to its dissemination. Yet it occasionally springs up independently 
in the opposite breast ; and I have elsewhere 3 reported a case of this kind. 

I have also there cited several remarkable instances in which, many 
years after extirpation of one breast for cancer without recurrence, the 
disease subsequently supervened in the opposite breast. 

Other instances of bilateral malignant disease of the breast, in which 
the concomitant tumours were of different anatomical structure, may 
also be mentioned in this category. 

Thus, Lebert 4 long ago described an example of colloid cancer of one 
breast, concomitant with ordinary scirrhus of the other. 

In like manner, Nunn 5 has met with tubular cancer of the left breast, 
coexisting with atrophic acinous cancer of the right breast : Mandry 6 
and Kiister 7 have had similar finds. 

Instances of scirrhous cancer of one breast, concomitant with sarcoma 

My book on " Diseases of the Breast," 1894, p. 318. 

Deutsche Chir., Lief, xli., S. 27. 3 " Diseases of the Breast," 1894, p. 302. 

Arch. f. path. Anat., Bd. iv., S. 216. 

Transactions of the Pathological Society, London, 1890, vol. xli., p. 224. 
Beitr. z. klin. Chir., 1892, Bd. viii., S. 589. 

Cited in Michelsohn's Inaug. Diss. " Zur Multiplicity der primaren Carcinomen," 
Berlin, 1889. 



300 THE NATURAL HISTORY OF CANCER 

of the other, have been described by De Morgan, Czerny, Bryant, and 
Billroth.i 

Ovary. Malignant tumours of the ovaries are often bilateral in origin. 
This is especially the case with sarcomatous kinds, a large proportion of 
which occur in early life : thus of 23 ovarian sarcomata studied by Pick, 
9 were bilateral of which latter, 6 were of the small round-celled variety. 
Examples of bilateral glandular ovarian cancer have been studied by 
Woolley, 2 Nicholls, 3 and others ; while, in a patient aged seventy, Fran- 
genheim 4 met with glandular cancer of both ovaries, together with endo- 
thelioma of the dura mater. Here also mention may be made of 
Ladinski's 5 remarkable case of glandular cancer of one ovary, with 
sarcoma of the other, in a patient with absence of the uterus, vagina, 
and tubes. 

Examples of the development of cancer in the sound ovary, after 
the removal of its cancerous fellow, have been reported by Le Gemtel 6 
and others. 

With regard to the initial multiplicity of non-malignant ovarian 
tumours, I need only mention that it is of frequent occurrence, especially 
in the dermoid, papillary and cystic forms. 

Here it seems desirable to mention, that bilateral malignant ovarian 
tumours are fairly often met with, as the result of dissemination from 
primary growths situated in the stomach, intestines, other abdominal 
viscera etc. ; and it is probable that some of the bilateral ovarian growths, 
called " Krukenberg's tumour," are really of this nature. 

In this connexion it should also be borne in mind, that secondary 
malignant ovarian disease is relatively much more frequent than the 
primary form, especially in adults. On the other hand, post-mortem 
records show, that gastro-intestinal cancers seldom disseminate in the 
ovaries. 

Testis. It is by no means very rare, for malignant tumours of the 
testis to be bilateral in origin ; and this seems to be of more frequent 
occurrence with the -round- celled sarcomata, than with other forms of 
the disease. 

A considerable proportion of these malignant testicular tumours, arise 
in infancy and early life ; and many of them are congenital. 

In a remarkable congenital case reported by Rogers, both testes, 
which had not descended, were sarcomatous, causing a large intra- 
abdominal tumour, which proved a serious obstacle to delivery. 

Malignant testicular tumours, especially those of early life, are 
remarkable for the great frequency with which heterotopic structures 
such as cartilage, bone, striped muscle etc. occur in them. 

Of 15 early- life testicular malignant tumours tabulated by Schubert, 
3 were bilateral ; and of 93 cases mostly adults analysed by Kober, 
5 were bilateral. 

For abstracts, vide my book on " Diseases of the Breast," p. 307. 

Boston Medical and Surgical Journal, 1903, No. 1, p. 1. 

Montreal Medical Journal, 1903, p. 326. 

Arch. f. path. Anat., 1906, Bd. clxxxiv., S. 201. 

American Journal of Obstetrics, July, 1898. 

Butt, et Mem. Soc. Anat. de Paris, 1906, No. 6, p. 470. 



MULTIPLE PRIMARY CANCER 301 

Kidney. Malignant tumours of the kidney are decidedly rare, except 
in infancy and early life, when many cases are met with, a considerable 
proportion of which are congenital, and bilateral in origin. As pre- 
viously mentioned, 1 it was by studying a case of a bilateral renal sarcoma 
in a young infant, that the " rest " theory of tumour formation was 
suggested to Cohnheim. According to Paul, 2 about half of these early- 
life renal sarcomata are bilateral ; but Walker, 3 from an analysis of 141 
recorded cases, finds that this proportion of bilateral cases is much too 
high, only 10 of his cases being bilateral. 

Bilateral origin is, however, of much more frequent occurrence in 
early-life sarcomata, than in any of the malignant renal tumours of more 
advanced life, although bilateral forms of the disease are occasionally 
met with even then ; thus, in an epileptic, male idiot, aged forty-four, 
Scheren 4 found a sarcomatous " mixed " tumour of each kidney, together 
with cylinder-celled cancer of the stomach, and multiple psammo- 
sarcoma of the brain. 

Adrenal. In infants and adults bilateral forms of malignant adrenal 
tumours are occasionally seen : Rolleston and Marks, in 26 tabulated 
cases at all ages, met with 2 instances of this kind. 

A case, which conclusively proves the bilateral origin of the disease, 
had been recorded by Breton and Looten. 5 

The patient, a woman aged fifty-seven, having suffered for some time 
from symptoms of adrenal insufficiency, with a painful intra-abdominal 
tumour, died suddenly. At the necropsy, each adrenal was enormously 
, enlarged by small round-celled sarcomatous growth, which had secon- 
darily invaded and caused enlargement of, each corresponding kidney, 
and the adjacent mesenteric glands. No other organs were involved. 
Similar cases have been reported by Frankel, 6 Woolley, 7 Suchardt and 
others. Adenoma of both adrenals has also been met with. 8 

Eye. Choroidal sarcomata are occasionally bilateral : this was so in 
5 of 214 cases studied by Fuchs. 

With glioma of the retina bilaterality is of more frequent occurrence, 
and many congenital cases of this kind have been reported indeed, con- 
genital glioma is usually bilateral. Of 60 cases of glioma retinse analysed 
by Lawford and Collins, in 12 the disease appeared to be bilateral in 
origin ; of Hirschberg's 60 cases, 14 were bilateral ; and of Wintersteiner's 
405 cases, 97 were bilateral. 

Brault has met with bilateral congenital ocular lipoma. 

Ear. Instances of the bilateral outbreak of epithelioma of the external 
ear, have been described by Mandry 9 and Sumpter. 10 In the latter's 
patient, " cancer " of the lip had been extirpated nine years previously, 
without recurrence. In all these cases the malignant disease supervened 
on chronic eczema of the part. 

1 Chapter VII. 2 Liverpool Med.-Chir. Journal, January, 1898. 

3 Annals of Surgery, 1898, vol. xxvi., p. 529. 

* Cited by Walter ( Arch. f. klin. Chir., 1896, Bd. 53). 

5 Le Nord. Med., August 15, 1905. 6 Arch. f. path. Anat., Bd. ciii., S. 244. 

7 Boston Medical and Surgical Journal, 1903, No. 1. 

8 Warthin, Arch, of Pediatrics, 1901, p. 812. 

9 Beitr. z. klin. Chir., 1892, Bd. viii., S. 589. 

10 Lancet, 1893, vol. i., p. 887 ; also ibid., 1894, vol. i., pp. 1160 and 1274. 



302 THE NATURAL HISTORY OP CANCER 

Extremities. Of 263 cases of primary cancer of the extremities 
analysed by Michael, 1 two were bilateral and approximately symmetrical : 
in one of these cases the cancerous disease supervened on chronic varicose 
ulcers. 

Massen has reported bilateral congenital myxosarcoma of the gluteal 
region. 

It is evident from these notes, that the bilateral outbreak of malignant 
disease in paired organs, is less exceptional than is generally believed, even 
when liberal allowance has been made for possible sources of error. 

Other Examples of Primary Multiplicity. 

Skin. In no part of the body does the initial outbreak of cancer, so 
frequently manifest itself in the form of multiple foci, as in the skin 
especially the skin of the face. In these cases, hyperplastic changes of 
the integument or other lesions, almost invariably coexist ; and workers 
in certain irritating substances such as tar, paraffin, soot etc., are rela- 
tively often affected. 

I have elsewhere 2 described the case of an asphalter, aged seventy-two, 
with three widely-separated, independent cancerous lesions on different 
parts of the face, associated with " chronic seborrhcea." 

Two of these lesions were ordinary epidermoidal cancer, while the 
third was cylinder-celled, sweat-gland cancer. 

Similar cases have been reported by Volkmann, 3 Tillmanns, 4 Schim- 
melbusch, 6 and others. In chimney-sweeps I have seen the scrotal 
integument similarly affected. Tillmans has met with an instance of 
epithelioma of the integument of the forearm and of the scrotum, in a 
paraffin worker. In old persons, multiple cutaneous cancers sometimes 
arise in connexion with chronic seborrhcea. Primary multiplicity is also 
often met with in cases of rodent ulcer, 6 especially in aged subjects ; and 
Bowlby 7 has seen six distinct lesions of this kind in one patient. 

Examples of multiple cancer of the skin of the face, supervening on 
lupous ulceration, have been recorded by Steinhauser, Bayha and others. 
It will be noticed that in most of the cases just mentioned, the outbreak 
of the cancerous disease appears to have been precipitated by some form 
of antecedent lesion ; which, it may be surmised, acted as fuel to the fire 
of pre-existing epithelial proliferation. 

Schimmelbusch has described epidermoidal cancer of the skin of the 
nape of the neck, concomitant with the same kind of cancer of the skin 
of the ear ; also the same kind of cancer of the ear and lower Hp. 

Tillmanns, in like manner, found the skin of the scrotum and forearm 
concurrently affected ; and C. Thompson 8 the skin of the scrotum, thigh 
and calf of one leg. Beatson 9 met with rodent ulcer of the face, in 

Beitr. z. Jdin. Chir., Bd. vii., S. 13. 

Twentieth Century Practice of Medicine, 1898, vol. xvii., p. 228. 

Sam. klin. Vortrage, No. 257. * Deutsche Zeits. f. Chir., 1880. 

Arch. f. klin. Chir., 1880. 

For cases, vide Hutchinson's " Archives of Surgery," 1891, vol. iii., pp. 318 and 335. 

Transactions of the Pathological Society, London", 1894, vol. xlv., p. 163. 

8 Practitioner, October, 1899, p. 414. 

9 British Medical Journal, 1899, vol. ii., p. 1602. 



MULTIPLE PRIMARY CANCER 303 

association with epidermoidal cancer of the skin of one hand, and 
cutaneous papilloma of the other hand ; Winiwarter, 1 three years after 
excision of epidermoidal cancer of the lower lip, without recurrence, found 
cutaneous cancer of the root of the nose ; and Becker 2 met with rodent 
ulcer of the left ala nasi, and similar disease of the right ear, together 
with melano-sarcoma of the right cheek, the patient being also affected 
with congenital angiomaof the left cheek, pigmen ted hairy mole of the fore- 
head, as well as with comedones, chronic seborrhoea, acne of the face etc. 

Many examples of primary multiple sarcoma of the skin have also 
been recorded in children and adults, several of the former being con- 
genital (Karewski etc.) ; but, the whole subject of sarcoma of the skin, 
and its relation to other morbid conditions, is in such a confused and 
unsatisfactory condition, that I must be excused from entering further 
into the matter here. 

As examples of the outbreak of the disease concurrently in the 
integument and other parts of the body, the following cases may be 
mentioned : epidermoidal cancer of the skin of the foot, with columnar- 
celled cancer of the gastric mucosa by Cordes ; 3 epidermoidal cancer of 
the skin of the abdomen, and cancer of the pyloric mucosa by Hutchin- 
son ; 4 I have seen rodent ulcer of the face, in a man from whose lower lip 
epidermoidal cancer had been excised fifteen years previously, without re- 
turn of the original disease ; cancer of the stomach, in a man whose ear had 
previously been extirpated for epidermoidal cancer, by Billroth ; 5 epider- 
moidal cancer of the skin of the face, with spheroidal-celled cancer of the 
pyloric mucosa, by Klebs ; 6 epidermoidal cancer of the skin of the upper 
eyelid, with cylinder-celled cancer of the rectal mucosa, by Kaufmann ; 7 
rodent ulcer of the face of fourteen years' duration, with sarcoma of the 
antrum of the superior maxilla by Langton 8 etc. 

Uterus. In the uterus, as in most other parts of the body, the 
initial manifestation of cancer is nearly always solitary ; but a few 
instances of primary multiplicity have lately been recorded. 

Thus Hofmeier, Winter, Schauta and Binswanger have reported cases, 
in which epidermoidal cancer of the portio, was concomitant with 
cylinder-celled glandular cancer of the corpus or cervix ; John Williams 
met with an instance, in which two separate columnar-celled glandular 
cancers of the canalis cervicalis, were associated with epidermoidal cancer 
of the portio ; while Hitschmann, Kaufmann, Lewers and others have 
found epidermoidal cancer of the corpus (including ingrowths and 
"nests"), combined with cylinder-celled adeno-carcinomaof the same part. 

The infantile type of uterine sarcoma is generally congenital, and 
multiple ab initio ; and, even among adult forms of uterine sarcoma, 
primary multiplicity is occasionally seen, especially in those of mucosal 
origin. 

Examples of concomitant uterine epithelioma and sarcoma, have 

" Beitr. z. Stat. d. Carcinom.," 1878. 2 Beitr. z. klin. Chir., Bd. xiv., S. 146. 

Arch. f. path. Anat., 1896, Bd. cxlv., S. 422. 

" Archives of Surgery," vol. iii., p. 47. 

Cited by Mercanton (Rev. Mid. de la Suisse rom., 1893, No. 3, p. 173). 

Arch. f. path. Anat., Bd. cxl. 7 Ibid., 1879. 

St. Bartholomew's Hospital Reports, 1888, vol. xxiv., p. 284. 



304 THE NATURAL HISTORY OF CANCER 

been recorded by Montgomery, Niebergall, Keller, Emanuel, Rabl- 
Riickhardt, Franque and others. 

In Montgomery's 1 case, cancer of the cervix was associated with 
sarcoma of the corpus ; while in Niebergall's, 2 both forms of malignant 
disease were present in the corpus, together with myoma and mucosal 
polypi. Milford 3 had previously described an instance of concomitant 
melanotic, myxomatous, myomatous and cystic uterine tumours. 

I have elsewhere 4 given examples of multiple malignant uterine 
growths, due to the spread of the disease by auto-implantation and 
dissemination. 

Cases illustrating the independent outbreak of cancer in the breast and 
uterus, have been carefully studied by Richter, 5 Beadles, 6 Young, 7 Mer- 
canton 8 (three cases), Broca 9 etc. 

Richter's and Beadle's patients were concurrently affected with 
epidermoidal cancer of the cervix uteri, and acinous glandular cancer of 
the mamma. In a case of this kind by Walter, 10 ovarian cystoma was 
also present. 

Russell (of Baltimore xl ) has described cases in which after vaginal 
hysterectomy for cancer without local recurrence cancer of the breast 
subsequently developed independently. 

The independent outbreak of cancer in the breast, uterus, and ovary 
has been signalized by Walter ; 12 in the vulva, breast and uterus by 
Zeiss ; 13 in the uterus and vagina by Mercanton; 14 in the uterus and vulva 
by Mercanton ; in the uterus and Fallopian tube by Hafbauer ; 16 in the 
uterus and ovaries by Reichel 16 and others ; in the uterus (epidermoidal 
cancer of the cervix) and pancreas (cylinder-celled glandular cancer) by 
Bard ; 17 the same variety of uterine cancer, concomitant with cylinder- 
celled cancer of the sigmoid colon by Beck ; 18 in the uterus (epidermoidal 
cancer) and thyroid (adeno-carcinoma) by Richter ; 19 in the uterus and 
stomach by Walshe, 20 Kronig 21 etc. 

An elderly lady, one of whose eyes had been extirpated by Hutchin- 
son 22 for melanotic sarcoma, died free from any return of the original 
disease ten years afterwards, of cancer of the uterus. 

Hanot 23 found cancer of the liver, coexisting with sarcoma of the 
uterus ; Schmincke, 24 cylinder-celled cancer of the gall-bladder, likewise 
with sarcoma of the uterus ; and Luminezen sarcoma of the vagina, with 
epithelial cancer of the uterus. 25 

Mamma. An example of epidermoidal cancer of the nipple, with 

1 Occidental Medical Times, 1893, p. 311. 2 Arch. f. Gyn., Bd. 1., Heft 1, S. 129. 

3 New Smith Wales Medical Gazette, 1873-1874, vol. iv., p. 163. 4 Chapter VIII. 

6 Wien. klin. Woch., August 17, 1905, S. 865. 

6 Transactions of the Pathological Society, London, 1897, vol. xlviii., p. 236. 

7 Archives of the Middlesex Hospital, 1904, vol. iii., p. 165. 

8 fiev. Med. de la Suisse Somande, 1893, No. 3, p. 173. 

9 " Traite des Tumeurs," 1866, t. i., p. 284. 10 Arch. /. Jclin. Chir., 1896, Bd. liii. 
11 Johns Hopkins Hospital Bulletin, December', 1899. 12 Op. cit. 

*3 Cent. f. Gyn., 1892, No. 40. 1J Op. cit. 

15 Arch. f. Gyn., Bd. Iv., S. 316. 16 Zeits. f. Geb. u. Gyn., 1880, Bd. xv. 

17 Arch. gin. de Med., 1892, p. 541. 18 Prag. med. Woch., 1883. 

19 Op. cit. 20 " Nature and Treatment of Cancer," 1846. 

21 Cent. f. Gyn., 1902, No. 30. 22 Archives of Surgery, vol. iii., No. 9, p. 48. 

2 3 Cited by Bard. 24 Arch. f. path. Anat., 1906, Bd. clxxxiii., S. 160. 

25 Pest. med. chir. Presse, 1878, xiv., p. 176. 



MULTIPLE PRIMARY CANCER 305 

concomitant acinous glandular cancer of the same breast, has been 
recorded by Morestin ; l and some cases of so-called " Paget's disease," 
undoubtedly belong to the same category. 

In a single breast, mixed malignant tumours comprising sarcomatous 
and epitheliomatous elements have also been reported (Heurtaux, Coen 
etc.), to which reference has been made in a previous chapter. 2 

I have elsewhere 3 recorded the case of an elderly woman who, having 
suffered for seven years from " rodent ulcer " of the face, then developed 
cancer of the mammary gland. She was also subject to uterine myo- 
mata. Hutchinson 4 has met with similar cases of the concomitancy of 
mammary cancer with rodent ulcer of face. 

Bryant 5 and Michelsohn 6 have seen scirrhous cancer of the breast, 
concomitant with epidermoidal cancer of the nose (three cases) ; and the 
former has met with cancer of the breast associated with cesophageal 
epithelioma. 

Panas 7 mentions the case of a man with scirrhous cancer of the breast, 
from whose lower lip epithelioma had been excised fifteen years pre- 
viously ; and similar cases have been recorded by Young and Wini- 
warter ; while Graviller 8 has seen cancer of the male breast, concomitant 
with epidermoidal cancer of the lower lip. 

A patient of Dobson's, 9 who had remained well and free from any 
return of the disease for six years after amputation of the breast for 
cancer, then developed epidermoidal cancer of the tongue, of which she 
soon died ; another patient of the same surgeon, two years after extirpa- 
tion of the breast for cancer, of which there was no return, died of small 
round-celled sarcoma of the tonsil. 

Gibson 10 has recorded the case of an old woman, who died of cancer 
of the pylorus, more than twenty years after extirpation of the right 
breast for cancer ; Poulsen's patient died of cancer of the stomach, five 
years after extirpation of the breast for the same disease ; Nicholls u has 
described cancer of the pyloric mucosa, with acinous glandular cancer of 
the mamma ; and Fraenkel 12 acinous cancer of the left mamma, with 
cylinder-celled cancer of the colon. 

Guende 13 met with sarcoma of the choroid in a woman, the subject of 
mammary cancer ; Nehrkorn 14 sarcoma of the vagina, with mammary 
cancer ; and Schael 15 scirrhus of the mamma, with spindle-celled sarcoma 
of one ovary. 

I have elsewhere 18 cited instances of associated mammary and ovarian 
cancer ; Cutler 17 has met with cancer of various thoracic and abdominal 

1 Arch. Gen. de Med., April 21, 1903. 2 Chapter VII. 

3 My book on " Diseases of the Breast," 1894, p. 304. 
* Archives of Surgery, vol. iii., No. 9, p. 147. 

6 " Diseases of the Breast," 1887, p. 340. 6 Inaug. Diss., Berlin, 1889. 

7 Cited by Poirier, " Tumeurs du sein chez 1'horame," Paris, 1883, p. 98. 

8 Canadian Medical and Surgical Journal, Montreal, 1873, p. 271. 

9 Bristol Med.-Chir. Journal, December, 1889. to Lancet, 1896, vol. ii., p. 225. 

II Montreil Medical Journal, 1903, vol. xxxii., p. 326. 
12 Munch, med. Woch., 1901. 

*3 Marseille Med., 1890, No. 7, p. 326. 14 Munch, med. Woch., 1901. 

16 Cited by Wells (Journal of Pathology and Bacteriology, June, 1901). 
18 " Diseases of the Breast," 1894, p. 306. 

17 Boston Medical and Surgical Journal, 1892, p. 329. 

20 



306 THE NATURAL HISTORY OF CANCER 

organs, with sarcoma of the ovary ; and Kesteven l found that cancer of 
the rectum and sarcoma of the femur developed in a patient, from whom 
recurrent mammary cancer had been extirpated six years previously, 
without any local recurrence. 

Gastro-intestinal Tract. Multiple primary malignant growths are 
met with more frequently in this system, than in any other part of the 
body, except the skin. I have previously referred to cases of multi- 
plicity due to auto-implantation in this locality ; and dissemination is 
another complication to be weighed, in estimating the validity of claims 
to initial multiplicity. 

Instances of this kind have been reported as occurring in all parts of 
this tract, from the lips to the anus. 

As examples, the following may be mentioned : triple epidermoidal 
cancer of the tongue (Hayward and Henderson 2 ) ; epithelioma of tongue, 
with sarcoma of epiglottis (Schiller 3 ) ; double cancer of the oesophagus 
(Bucher 4 ) ; epidermoidal cancer of the tongue, with double cancer of the 
oesophagus (Richter 5 ) ; round and spindle-celled sarcoma with epider- 
moidal cancer, both of the lower part of the oesophagus (Frangenheim 6 ) ; 
epidermoidal cancer of the tongue with columnar-celled (colloid) cancer 
of the jejunum (Abesser 7 ) ; epidermoidal cancer of the oesophagus and 
stomach (Borst 8 ) ; epidermoidal cancer of the oesophagus, with cylinder- 
celled cancer of the pyloric glands (Rosenbach 9 ) ; epidermoidal cancer of 
the oesophagus, with cylinder-celled cancer of the ampulla of Vater 
(Courmont 10 ) ; cylinder-celled cancer of the pylorus, with colloid cancer of 
the caecum two cases (Orth and Beck n ) ; multiple cancer of the ileum 
(cases by Lubarsch 12 and Bunting 13 ) ; multiple cancer of the jejunum 
(Notthaft 14 ) ; cancer of ileum and lower part of the rectum both of 
columnar type (Robson and Knaggs 15 ) ; multiple cancer of the large 
intestine and rectum (cases by Rutherford, Teacher and Buchanan 16 ) ; 
cylinder-celled cancer of the rectum and sigmoid colon with multiple 
polypi (Morton 17 ) ; cylinder-celled cancer of rectum and splenic flexure of 
colon with multiple polypi (Handford 18 ) ; cancer of the stomach and 
colon (Bucher 19 ) ; double cylinder-celled cancer at opposite ends of the 
rectum, with multiple polypi (Robson and Knaggs 20 ) etc. 

The subjects of malignant disease of the gastro-intestinal tract, may 
also develop the malady independently in other parts of the body, of 

1 Clinical Society's Transactions, London, vols. vi. and ix. 

2 Lancet, 1901, vol. ii., p. 22. 3 Berlin, klin. Woch., 1898. 
4 Ziegler's Beitr. z. path. Anat., Bd. xiv., Heft i., S. 100. 

6 Wien. klin. Woch., 1905, S. 865. 6 Arch. f. path. Anat., 1906, Bd. 184. 

7 Cited in Michelsohn's I. D. " Zur Multiplicitat der primaren Carcinomen." Berlin, 
1889. 

8 " Die Lehre von den Geschwiilsten," 1902, Bd. ii., S. 773. 

9 Arch. f. path. Anat., 1905, Bd. clxxix., S. 567. 

10 Lyon Med., April 15, 1894. 

11 Cited by Bard (Arch. Gen. de Med., 1892, i., p. 541). 

12 Arch. f. path. Anat., 1888, Bd. cxi. 

13 Johns Hopkins Hospital Bulletin, December, 1904, p. 389. 

14 Deutsche med. Woch., October 22, 1896. Lancet, 1905, vol. i., p. 640. 

16 Transactions of the Pathological Society, London, 1905. 

17 Lancet, 1895, vol. i., p. 1145. 

18 Transactions of the Pathological Society, London, 1890, vol. xlv., p. 133. 

19 Ziegler's Beitr. z. path. Anat., Bd. xiv. 20 Op. cit. 



MULTIPLE PRIMARY CANCER 307 

which many instances have been already cited in this chapter, and to 
these the following may be added : cylinder-celled cancer of the mucosa 
of the colon with epidermoidal cancer of the vulva by Chiari ; x cancer of 
the pyloric mucosa with epidermoidal cancer of the skin of the right ear 
by Hauser ; 2 cancer of the colon, rectum and right adrenal by Zimmer- 
mann ; 3 colloid cancer of the caecum, with epidermoidal cancer of the soft 
palate by Frangenheim ; 4 adeno-carcinoma of colon, with malignant 
cystoma of left ovary by Richter ; 5 carcinoma of stomach, with glioma 
of cerebrum by Hansemann ; 6 cylinder-celled cancer of the stomach, with 
spindle-celled sarcoma of one ovary, by Buchnell and Hinds ; 7 cancer of 
the stomach of " adenoid type," round-celled sarcoma of the right testis, 
with endothelial sarcoma of the dura mater ; 8 cancer of the stomach and 
bladder by Szumann ; 9 epidermoidal cancer of the oesophagus, with endo- 
theliomata of the dura mater by Kretz ; 10 epidermoidal cancer of the 
oasophagus, with spindle-celled sarcoma of the stomach by Thierfelder ; n 
epidermoidal cancer of the anus, with villous cancer of the bladder by 
Nehrkorn ; 12 columnar-celled cancer of the rectum, with epidermoidal 
cancer of the larynx, has also been described by Butlin. 13 

Many examples of concomitant gastric and ovarian cancer have been 
reported ; as also of gastric cancer with ovarian fibro-sarcoma, endo- 
thelioma etc. (Krukenberg's tumours); intestinal cancer has also often been 
found associated with similar ovarian lesions : I have elsewhere 14 referred 
more fully to cases of this type. 

Instances of the concomitant association of sarcoma of the choroid, 
with malignant epithelial tumours in other parts of the body, have been 
described by Parsons, 15 Fischer and Bosc. 

From such examples as the foregoing, which by no means exhaust the 
list, the following conclusions may be drawn : 

1. The fact of the occurrence of multiple outbreaks of malignant 
disease is thus clearly established, both for individual organs, for paired 
organs, and for different parts of the body. 

2. It is further established, that although primitively multiple malig- 
nant tumours are generally of the same kind ; yet, in many instances, 
they are generically different (e.g., epithelioma and sarcoma) : and even 
when the multiple growths are of the same genus (e.g., epitholioma) they 
may be of different varieties (e.g., colloid cancer of one breast and scirrhus 
of the other etc.). 

3. Multiple outbreaks of malignant disease are probably less excep- 
tional than is generally believed, the evidence to this effect being especially 
strong in the case of paired organs. 

Cited by Bard. 2 Arch. f. path. Anat., 1894. Bd. cxxxviii., S. 402. 

Canadian Journal of Medical Sciences, Toronto, 1882, vol. vii., p. 390. 
Arch. f. path. Anat., 1906, Bd. clxxxiv., S. 201. 

Wien. klin. Woch., 1905, S. 865. Zeits. /. Krebsforsch., i., p. 3, S. 183. 

British MedicalJournal, 1905, vol. ii., p. 1115. 

Cited by Beadles (Transactions of the Pathological Society, London, 1897, vbl. 
xlvi ., p. 236). 

Cited bv Bard. 1 Cited by Walter (Arch. f. klin. Chir., Bd. liii., 1896, S. 1). 

Ibid. " 12 Munch, med. Woch., 1901. 

13 British Medical Journal, 1905, vol. ii., p. 1570. 

14 Chapter XIX. 15 " Pathology of the Eye," 1905, vol. ii., p. 497. 

202 



308 THE NATURAL HISTORY OF CANCER 

4. Initial multiplicity is relatively often concomitantywith certain 
structural derangements, which may be presumed to give predisposition 
thereto. These derangements comprise pre-natal developmental irregu- 
larities, especially obvious in the early-life, bilateral forms of multiplicity ; 
local hyperplastic lesions, such as chronic seborrhoea, chronic eczema, 
lupus, and the effects of various irritants such as soot, tar, paraffin etc., 
especially obvious in cutaneous manifestations ; in the gastro-intestinal 
system, such lesions as multiple polypi ; and, in the breast, the puerperal 
state. In the uterus, conditions of this kind are less obvious ; but they 
may, nevertheless, exist. 

5. Taken in their entirety, these various considerations point to some 
* general systemic change, as the predisposing cause of primary 7multi- 

plicity. 

The Question of Mixed Malignant Tumours. 

The question of the existence of mixed malignant tumours, that is to 
say, of tumours in which sarcomatous and epitheliomatous processes go 
on concurrently, is perhaps as yet hardly ripe for dogmatic treatment, 
by reason of the paucity of well-recorded facts relating thereto. 

On a jyriori grounds, however, no objection need be raised to this 
conception ; while some significant facts can be cited in its favour. 
Referring to this matter, Virchow 1 says : " There are true mixed forms 
of sarcoma and carcinoma tumours of which certain parts are sarco- 
matous, while others are carcinomatous." 

In support of this dictum, reference may be made to several cases in 
the foregoing list, in which two different kinds of malignant growth were 
found concurrently in certain organs, either as two separate tumours, 
or more or less fused into a single tumour (sarco-epithelioma). 

Thus, in Frangenheim's case, we see at the lower end of the oesophagus 
a round- and spindle-celled sarcoma, and so closely contiguous to it as to 
form but a single morbid mass epidermoidal cancer. 

Then, in the mamma, we have instances in which the two kinds of 
malignant disease are so closely combined, as together to form but a 
single tumour, as in Heurtaux's case of glandular cancer with ossifying 
and chondrifying sarcoma, which I have elsewhere 2 fully detailed ; more- 
over in this case, the secondary growths reproduced all the peculiarities 
of the primary mixed tumour. 

In other parts of the body similar instances have been reported, 
especially in connexion with the malignant tumours of infancy and early 
life : thus, Kaposi 3 has described two examples of " sarco-carinomatous " 
tumours of the face of girls, aged respectively ten and seven years, who 
had suffered from earliest infancy with xeroderma of the part ; and 
Lapointe and Lecene 4 the same type of disease in the right adrenal of 
an infant nineteen months old etc. 

Maier 5 has described a thyroid tumour from a woman aged forty, in 

1 " Die krankhaften Geschwiilste," 1863. 

2 My book on " Diseases of the Breast," p. 170. 

3 Hebra's " Skin Diseases," Sydenham Society's Translation, vol. iii., p. 254 ; and 
vol. iv., p. 222. * Butt, et Mem. Soc. Anat., Paris, November. 1904. 

6 Arch. f. path. Anat., 1877, Bd. Ixx., S. 378. 



MULTIPLE PRIMARY CANCER 309 

which ossifying and chondrifying sarcoma and carcinoma were combined ; 
and other instances of thyroid sarco-carcinoma have been reported by 
Donati, Syme, Schmorl, Kaufmann, etc. ; while Wells, 1 Loeb, and Rum- 
mer 2 have likewise met with this combination in thyroid tumours of dogs. 

It is, however, in the uterus that the most numerous and best studied 
examples of this kind of morbid growth have been found. 

Some of the cases to be cited in this connexion have been adversely 
criticized ; but, in my opinion, their validity has not been impaired. 

I have previously referred to the remarkable cases of Niebergall and 
Milford, in which two different forms of malignant disease were present 
in the same uterus, together with various non-malignant growths. 

Then there is Montgomery's case, in which glandular epithelioma of 
the cervix was concomitant with sarcoma of the corpus. 

In Keller's 3 case, a round and spindle-celled polypoid sarcoma of 
the cervix was associated with glandular epithelioma of the same part. 

Emanuel 4 found a round-celled, polypoid sarcomatous tumour, grow- 
ing from the wall of the corpus, concurrently with diffuse glandular 
epithelioma of the mucosa of the same part. 

In Abel and Landau's 5 case, glandular epithelioma of the cervix was 
associated with diffuse sarcoma of the uterine mucosa. 

In Rabl-Riickhardt's 6 patient, after a polypoid, sarcomatous tumour 
had been spontaneously expelled from the uterus, the mucosa was then 
found to be affected with diffuse glandular cancer. At several points, 
cancerous glandular ingrowths from the overlying diseased mucosa, had 
penetrated into the sarcomatous tumour. 

Franque's 7 three cases may next be cited : in the first of these, round- 
and myeloid-celled sarcoma of the mucosa of the corpus, was concurrent 
with glandular epithelioma of the cervix ; in the second, cylinder-celled 
glandular epithelioma of the corpus was present, together with round- 
celled sarcoma of the adjacent part of the cervix, the two morbid growths 
being quite distinct, though contiguous ; and, in the third, sarcoma of 
the uterine wall was concomitant with glandular epithelioma of the 
cervix. 

Finally, mention may be made of H. Spencer's 8 case, in which glan- 
dular epithelioma of the corpus, was concurrent with small round-celled 
sarcoma of the same locality. 

Similar series of cases have been reported in connexion with the ovary. 

It requires no great stretch of the imagination to see how, from the 
fusion of closely contiguous growths of different kinds, such as the fore- 
going series reveals, true mixed tumours may result, of which an example )\ 
has been reported by Rosenstein 9 in the uterus ; and, in other parts 
of the body, by Fletcher, 10 Maier, 11 Kuhnart 12 and others. 

Journal of Pathology and Bacteriology, 1901, vol. vii., p. 352. 

Bev. Mid. de la Suisse Romande, 1898, t. viii., p. 703. 

Zeits. f. Geb. u. Gyn., 1890, Bd. xx., S. 116. * Ibid., 1896, Bd. xxxiv., S. 1. 

Arch. f. Gyn., Bd. xxxii., xxxiv., and xxxv. 

Beitr. z. Geb. u. Gyn., 1872, Bd. 1., S. 76. 

Zzits. f. Geb. u. Gyn., 1899, Bd. xl., S. 183. 

8 Transactions of the Pathological Society, 1906; also Lancet, 1905, vol. ii., p. 1109. 

9 Arch. f. path. Anat., 1883, Bd. xcii., S. 191. 

10 Transactions of the Pathological Society, London, 1902, vol. lii., p. 199. 

11 Arch. f. path. Anat., Bd. Ixx., S. 378. " 12 Arch. f. Gyn., 1874, Bd. vi. 



310 THE NATURAL HISTORY OF CANCER 

Although the histological and some of the general biological char- 
acters especially the reproduction of the original mixed type in the 
disseminative lesions of certain rare malignant growths seem to coun- 
tenance the belief in the existence of mixed malignant tumours, it must 
not be concluded on this account, that transitions from one type of 
malignant growth to another occur (transformation, metaplasia). Never 
have transitions of this kind been verified. This proposition rests on a 
mistaken apprehension as to the origin of the tissue cells, the specificity 
of which modern cytological studies have revealed. 

Thus, among neoplastic tissues, as among the normal tissues, there 
are no transitions from one specific type to another ; in fact, the meta- 
plasia of Virchow has no real existence. 



The Association of Malignant with Non-malignant Tumours. 

It not uncommonly happens that malignant and non- malignant 
tumours are associated, in the same individual, of which some remarkable 
examples have been cited above. 

" In further illustration of the subject, reference may be made to the 
case of a woman, aged fifty-two, who died after abdominal hysterectomy 
for uterine myomata, when Lubarsch 1 found sarcoma of the gall-bladder, 
a large adenoid polypus of the stomach, a small " tumour " in the spleen, 
lipoma of the right kidney, " struma suprarenahs aberrans," cystic 
kidneys and enchondroma of the right pleura. 

In Guy's Hospital Museum 2 is a specimen of cancer of the uterus, 
concomitant with adenoma of the right adrenal ; and Bosanquet 3 has 
found cancer of the stomach, with adenoma of both adrenals. 4 

Lubarsch 5 has met with cancer of the stomach, in association with 
multiple polypi and cystic adenoma of the part ; and, many instances 
of this kind have been reported, in the large intestine. Maier 6 encoun- 
tered enchondroma of the kidney, with cancer of the same ; and, enchon- 
droma of the subcutaneous tissue of the thorax, also with cancer. ^ 

De Santi 7 found fibroma papillare of the nasal septum, with rodent 
ulcer of the nose. 

Milian 8 epithelioma of the lung and cancer of the parotid, with 
adenomata of the liver. 

Many instances of the association of cancer of the liver with 
" adenoma " of the same, have also been reported (Schmieden, 9 Wells, 10 
Eggel u etc.) ; and in the thyroid this concomitancy is far from 
uncommon. ( 

Cited by Walter (Arch. f. klin. Chir., 1896, Bd. liii., S. 1). 

No. 2,020, Pathological catalogue. 

Transactions of the Pathological Society, London, 1902, vol. lii., p. 64. 

For other instances of concomitant adrenal tumours and cancer elsewhere, '. vide 



Cha 



pter 

Ar 



IX. 5 Cited by Walter. 



Arch. f. path. Anat. 1877, Bd. Ixx., S. 378. 
Lancet, December 8, 1894. 

Butt, et Mem. Soc. Anat., Paris.plarch 19, 1897. 
Arch. f. path. Anat., 1900, Bd. clix., S. 290. 

10 American Journal of Medical Science, 1903, p. 403. 

11 Ziegler's Beitr. z. path. Anat., etc., 1901, Bd. xxx., S. 506. 



ASSOCIATION OF CANCER WITH OTHER TUMOURS 311 

Smyly l found spindle-celled sarcoma of the lower end of the femur, 
concomitant with a large ossified enchondroma, and a lipoma, all of the 
same vicinity. 

Uterine myomata are often present in the cancerous as in the non- 
cancerous ; thus, of 79 necropsies for uterine cancer in my list, myomata 
were present in 5 or in 6-3 per cent., and in many cases mucosal polypi 
as well. 11-3 per cent, of my breast cancer cases, were subject to uterine 
myomata. As mentioned in the preceding chapter, in cancer of other 
localities, uterine myomata coexisted in 18-5 per cent, of the necropsies. 

Tate 2 has seen cylinder-celled epithelioma of the corpus uteri con- 
comitant with myomata of the same, and with myoma of the left ovary ; 
Cullen 3 found cancer of the corpus uteri, with multiple uterine myomata, 
and papillary cystoma of both ovaries. 

According to Chiari, 4 the subjects of uterine myoma are unduly 
prone to cancer. Of 25 women with myomata under his observation, 
2 had cancer of the uterus, 1 cancer of the breast, and 6 had cancer of 
other organs. This is a very slender basis on which to rest such a 
sweeping statement. If Chiari's views were correct, we should expect 
to find uterine myomata much more frequently in the cancerous than in 
the non-cancerous. But, of 159 female cancer necropsies in my list, 
uterine myomata were present in only 20, or in 12-5 per cent. ; whereas, 
according to Bayle, they are found in 20 per cent, of all women over 
thirty-five. Hence Chiari's conclusion must be rejected. 

In like manner ovarian cystomata oophoronic, parovarian and 
dermoid are fairly often found in association with malignant tumours : 
thus, of Lebert's 45 uterine cancer necropsies, ovarian cystomata were 
present in 3 ; and, of Winckel's numerous cases of ovarian cystomata, 
8 per cent, had also uterine cancer. 

Of 44 necropsies for mammary cancer in my list, ovarian cystomata 
were present in 3. 

The association of ovarian cystomata with malignant disease of other 
parts of the body, especially of the gastro-intestinal tract, is also an 
occurrence of no great rarity. 5 

Of 85 female mammary cancer patients in my list, fatty tumours were 
present in 2 ; one of these patients was also the subject of multiple 
molluscum fibrosum, an ovarian dermoid, and a mucous polypus of the 
cervix uteri. 

De Morgan and Murchison have each seen uterine cancer, associated 
with multiple lipomata of various parts of the body. 

1 Transactions of the International Medical Congress, London, 1881, vol. i., p. 114 
(specimen exhibited in museum). 

2 Transactions of the Obstetrical Society, London, 1905, vol. xlvi., p. 138. 

3 " Cancer of the Uterus," 1901, p. 463. 

4 " Klin, der Geburts.," etc. Erlangen, 1853. 

5 Lockyer (Practitioner, November, 1903), case of cancer of rectum with ovarian 
cystomata ; and Terrier ( Union Med., Paris, 1887, t. xliv., p. 5), sarcoma of transverse 
colon, with cystoma of right ovary. Deanesly (British Medical Journal, 1902, vol. i., 
p. 1148) and Boucher (New York Medical Secord, 1902, November 22, p. 816), cases of 
cancer of colon, with bilateral ovarian cystoma, etc. 



CHAPTER XIV 



THE INFLUENCE OF SEX 

THE influence of sex in determining the localization and incidence of 
tumours is very great ; and, it is noteworthy, that both malignant and 
non-malignant varieties are subject thereto. This seems to imply, that 
the conditions determining the growth of both varieties of tumours are 
the same in kind, and differ only in degree. 

In illustration of the subject, reference may be made to my analysis 
of 15,481 primary tumours of all kinds, consecutively under treatment 
at four large metropolitan hospitals, during a period of from sixteen to 
twenty-one years, as follows : 

TABLE SHOWING THE SEX INCIDENCE OF 15,481 PRIMARY TUMOURS. 





Total. 


Males. 


Females. 


Sex Ratio. 


Epithelioina i.e., malignant epithelial 
tumours 


7878 


2861 


5017 


1 to 1'75 


Sarcoma 


1350 


702 


648 


1 0'92 


Non-malignant tumours 


4613 


1179 i 3434 


1 2'91 


Cysts 


1640 


449 ! 1191 


1 2'65 




15,481 


5,191 


10,290 


1 T98 



The greater prevalence of malignant epithelial tumours among females, 
is entirely due to the frequency with which the mammae and uterus are 
affected, the corresponding structures in males very rarely originating 
the disease l ; while, in nearly every other locality, the male liability 
preponderates, as I have elsewhere pointed out. 2 

Hence sarcomatous tumours, which do not manifest this special pro- 
clivity to attack the female reproductive organs, are more equally dis- 
tributed between the sexes. 

My analysis also shows, that the relative proneness of females to 
non-malignant tumours and cysts, is even greater than it is to malignant 
epithelial tumours ; and, as a detailed examination of the matter indi- 
cates, this is attributable to the undue frequency with which in women 
the uterus and ovaries are attacked, the corresponding male organs 
seldom being affected by tumours of this type. 

An inference from the foregoing is, that we must seek for an explana- 

1 The national mortality returns, for 1900, show that the female cancer death-rate- 
less the mortality due to cancer of the mammary and generative organs was 583 per 
million, as against 660, the corresponding male rate. 

2 Chapter XVII. 

312 



THE INFLUENCE OF SEX 313 

tion of these remarkable diversities in morbid proclivity, in biological 
peculiarities inherent to the affected parts, and in their concomitant 
developmental and structural diversities all of which are ultimately 
ascribable to functional modifications rather than to any general con- 
stitutional condition correlated with sex. As mentioned in a previous 
chapter, the greater proclivity of human females to cancer, than the 
females of animals, is due rather to circumstances connected with the 
special sheltered environment of the former, than to any peculiarity 
connected directly with sex. It accords with this that of late when 
owing to urbanization the conditions of existence for men and women 
have been rendered less divergent the disparity in cancer proclivity has 
lessened, and this change is still in progress. Of like import is the great 
frequency of cancer in castrated animals of both sexes, to which I have " 
previously referred. 1 

We may also turn for information as to the influence of sex in malig- 
nant disease, to the national mortality returns. 

Thus, the Sixty-third Report of the Registrar-General, for the year 
1900, shows that among males the cancer mortality was 672 per million 
living of that sex, the corresponding figure for females being 975 : in the 
same year 26,721 persons died of the disease, of whom 10,475 were males 
and 16,246 females the sex ratio being 1 male to 1-5 females ; 1 male 
died of cancer to every 29 male deaths from all causes, and 1 female died 
of this disease to every 17 female deaths ; and finally, of persons aged 
thirty-five years and upwards, 1 in 15 men and 1 in 9 women died of 
cancer. 

For the year 1906, the respective cancer death-rates were 794 per 
million for males, and 1,032 for females, the sex ratio being 1 male to 
1-3 females. 

As I have elsewhere shown, 2 this increasing cancer mortality has 
affected males, to a much greater extent than females. In further illus- 
tration of this subject, the foregoing data may 'be compared with those 
derived from the massed national mortality returns for the twenty-five 
years 1848-1872, which show a sex ratio of 1 male to 2-29 females ; 
1 male having died of cancer to every 100 male deaths, and 1 female to 
every 41 female deaths. 

It seems likely, if the disproportionate increase of cancer among males, 
now going on in our country, continues unchecked, that the disease will 
eventually become more prevalent among men than among women, as 
is already the case in Australia and New Zealand ; thus, in 1900, the 
cancer death-rate for all Australia was 591 for males, as